BNA Bulletin Spring 07 - British Neuroscience Association

ulletinI N S I D Ea newsletter for members of the BNAGenetic models of migraineAlzheimer’s Disease: novel therapeutic targetsSecretary’s Report 3 Interview 4 Opinion 5-6 BNA News 7-16 BNA Events 17-19Scientific Reviews 20-24 Scientific Writing Prize 25-30 Meeting Reports 31-34Book Reviews 35 Noticeboard 36-37 Vacancies 37-38SPRING 2007 Issue 56

BulletinSECRETARY’S REPORT● Our Christmas Symposium held at the Royal Society was, asalways, well attended and very enjoyable. In addition to thewonderful science offered to us by an impressive line-up ofspeakers, the audience was also treated to a very strikingillustration of how research can be translated into effectivetreatments for the devastating conditions that affect thenervous system. Mike Robins, the recipient of the BNA Awardfor Public Service, gave a dramatic and personal demonstrationof how deep brain stimulation is alleviating the symptoms of hisParkinson’s disease. Mike made the point vividly thatsuccessfully translating research through to treatment can havea profound impact on the quality of people’s lives.● As we highlighted in the previous Bulletin, translationalresearch is being promoted by the Wellcome Trust, throughtheir newly initiated Masterclasses in Clinical Neuroscience. Atthat stage it was difficult to predict what the level of interest inrunning these courses from basic and clinical scientists wouldbe. However, it was clear from the response to the first call thatthere is a lot of enthusiasm for the scheme, with considerableinterest in having BNA as the partner learned society. Proposalswere submitted for a number of different clinical conditionsincluding motor neuron disease, stroke, traumatic brain injuryand autism. We look forward to supporting the first round ofMasterclasses and hope that the scheme will continue in orderto enhance interactions between basic scientists and cliniciansin a wide variety of clinical conditions.● By the time this Bulletin is published our National Meeting willbe almost upon us. The core of the meeting is, of course, theextensive scientific programme of plenary lectures, symposiaand poster viewing which the programme committee hopes willDEBBIE DEWARcover the interests ofthe majority of BNAmembers.However,there is a series ofspecial events thatshould appeal to thosealso interested in the other activities the BNA aims to promote,including neuroscience teaching, winning grants and careerpaths for junior scientists. The Public Awareness of ScienceGroup will host a café-bar discussion chaired by the Radio 4presenter, Quentin Cooper. At the last national meeting inBrighton, the café-bar forum proved to be a great way ofpromoting lively debate while relaxing with a drink after a day atthe meeting. Another special event has been organised tocommemorate the 10th anniversary of European Dana Alliancefor the Brain (EDAB) and will include discussions betweenneuroscientists and artists about how the two can interact. Nodoubt the free wine will help these discussions get under way.A free lunch should also be an added incentive to attend theAGM during the meeting and members are encouraged tocome along if they have views about the BNA they wish to air.If you haven’t already registered for the meeting, you canalways come along to Harrogate and do it on site.● I will be stepping down from the BNA Committee at theHarrogate meeting and this is my final contribution to theBulletin. It has been a fun being on the BNA committee and Iwould like to thank past and present colleagues for making itone of the few committee meetings I actually looked forward to.I am delighted to hand over the tasks of introducing thiswonderful publication and reporting on various BNA activities,to Colin Ingram, our new Honorary Secretary.A montage of low resolution images of human neuroblastoma (SH-SY5Y) cells responding to nicotine using Fura-2 calcium imaging. Two responses to the same dose of nicotine are shown. Shifts to the red end of the colourspectrum indicate a rise in intracellular calcium. Such experiments are being used to dissect the pathwayswhereby activation of nicotinic acetylcholine receptors protect neurones from amyloid toxicity in a hunt forpossible new drug targets for the treatment of Alzheimer’s Disease. See Steven Buckingham review (pages 22/23)DATES FOR YOUR DIARY: BNA EVENTS 2007● 1st – 4th April, 2007:19th National Meeting, International Centre,Harrogate, North Yorkshire, in association withNeuroscience Ireland● 9th May, 2007:One Day BNA-Promemoria Symposium andWorkshop: Functional Cellular Neuroimaging andMicroscopy, at The Open University, Milton Keynes● 27th June, 2007:Controversial Issues in Neuroscience: Talkingtherapies – all in the mind?, a café-bar discussionat The Dana Centre, London, SW7● 13th - 17th July, 2007:IBRO World Congress, Melbourne, Australia● 4th – 8th September, 2007:8th European Meeting on Glial Cells in Healthand Disease, at Imperial College, London● 26th September, 2007:Controversial Issues in Neuroscience: Mind wars,a café-bar discussion at The Dana Centre,London, SW7● 17th October, 2007:One Day Symposium: ‘Bench to bedside in acutestroke: ‘Finding our way’ or ‘Lost in translation?’,University of Edinburgh● 12th December, 2007:The Christmas Symposium, at The Royal Society,London, NW1The British Neuroscience Association Bulletin is published regularly and distributed to over 2,000 members of the BNA. Theviews expressed in the Bulletin are the authors’ own and are not necessarily the opinion of the BNA committee.DEADLINE FOR SUBMISSION OF ITEMS FOR THE NEXT BULLETIN: Ist JUNE 2007The BNA Bulletin is produced by Yvonne Allen in the BNA Conference Office, with assistance from Adam Koppel.Please send any items for inclusion in the next Bulletin to:Bulletin Editor, BNA Conference Office, The Sherrington Buildings, Ashton Street, Liverpool L69 3GETel: 0151 794 5449 / 4943 ✦ Fax: 0151 794 5516 / 5517 ✦ email: bulletin@bna.org.ukThe British Neuroscience Association is registered as a charity (1103852) and as a charitable company (4307833) ISSN 1475-8679ISSN 1475-86793

INTERVIEWOPINIONLaurie Pycroft is only 17 years old yet has alreadymade quite an impact since the founding barely twoyears ago of Pro-Test, a campaigning groupsupporting animal research for the advancement ofmedical and scientific discovery. He is clearly a verybusy young man, hence the brevity of his answers,but this succinct reply to the Bulletin at least gives usan insight into the thoughts and aspirations ofsomeone willing to take a stance in such anincreasingly vitriolic debate.GM, stem cells andnanotechnology –is neuroscience next?Science communicationin the 21st Century‘I have no regrets, and the few offensive e-mailsthat I do get really don't bother me’Laurie, can you tell us a little about yourself - have youalways lived in Oxford? What are your interests atschool? What do you hope to do at college/universityin the future?I actually live in Swindon, and have done since I was veryyoung, before which I lived in Holland, where I was born.I'm very interested in all areas of science, especiallyneuroscience, nanotechnology, anatomy, pharmacologyand various others, as well as computing. I hopeeventually to study medicine.What inspired you to form Pro-Test? What is the extentof this organisation now? Has its rapid growthsurprised you? Alarmed you?I formed Pro-Test as a result of the monopoly that the"animal rights" activists seemed to hold over the animalresearch debate. I felt it's important that people hear thefacts about animal testing. The speed at which Pro-Testhas grown has really surprised me, and I'm stillastounded by how successful we've been.This must be a major commitment for you now. Are youoften asked how you find time for your schoolwork?What do you say to this?4I'm actually not attending school at the moment- I'm takingsome time out to get some real-world work experience andto concentrate on working with Pro-Test.You have clearly mobilised much support for animalresearch. Do you feel satisfied? Is there more you wouldlike to achieve? Is there an 'end-point' to your campaign?I'm very glad with all that Pro-Test and other advocacygroups have achieved over the last year in the animalresearch debate, and I just hope that we are able to carryon spreading the truth. I don't think that there is a real endpointwhere Pro-Test is concerned, but eventually I do hopeto take a more hands-off role, so that I can engage inadvocacy of other issues.Do you have any regrets? How are you coping with theabuse from those opposed to your views? Has yourfamily been involved too? Are they supportive?I have no regrets, and the few offensive e-mails that I do getreally don't bother me. My family were initially quite worriedabout possible reprisals, but they've always been verysupportive, and we all feel a lot safer now.Is there anything you would like to say to BNA membersin particular? How can the BNA help you?I'd like to thank the BNA's members for improving thehealth of this country in spite of not being given the respectand pay that they deserve, and I'd especially like to thankall the nurses who attended both our demonstrations.Currently, we don't have any specific plans that we needhelp with, but please do keep supporting us, and if youwish to make a donation (always very appreciated!) thenplease go to our website (www.pro-test.org.uk).‘Good science communication is acollaboration, not a battle betweenpress and academia. Andresearchers find that using themedia gains wider recognition fortheir academic work, which in turnleads to international awareness,better research links with otherinternational institutions, andultimately gets them access togrant funding and collaborations’Putting a Factor 45 sunblock on your baby’s skin when you finallyget time for that much needed holiday in the sun seems asensible precaution. But you may not know that you are probablyusing nanotechnology, and the cream may contain tiny mirrorparticles so small that they could pass straight into your child’sskin cells, with all sorts of unknown future health implications.If you feed processed and pre-prepared baby foods to yourinfant, do you check to see whether it contains geneticallymodified soya extracts, or possibly dangerous pesticideresidues? And if you do check the labels and sources of theseproducts, do you understand the science enough to know whatrisks you are taking with your child’s health?I’d expect neuroscientists and other readers of BNA Bulletin tounderstand medical risks, pressure group hype, and the limitedconventions of newspaper reporting well enough to makeinformed decisions about these types of concerns. But does thepublic have sufficient information? And do the politicians andgrant bodies who decide on the funding and other resourceswhich will allow effective neuroscience research to continue inthe NHS and at academic institutions in the UK in the futureunderstand your current problems and needs?Of course, if you are a sophisticated reader of tabloids, ournational daily newspapers, you will understand the convention ofthe question mark in my title. Apart from its apparent mission totest every single substance in the universe and divide it intoeither cancer causing or cancer curing, the Daily Mail has madeone other great contribution to scientific debate – the questionmark headline.When a scientist writes ‘Does eating hedgehogs preventmigraines?’ then the answer is usually ‘Yes, our study seems toindicate so’. But when the Daily Mail writes a headline such as‘Is breakfast tea the cure for cancer?’ you can bet that theanswer is ‘No’. Otherwise the headline would read ‘Tea is thecure for cancer’. I am indebted to my friend, former Mail writerand current Daily Telegraph consumer affairs editor, DavidDerbyshire, for this succinct analysis and indicator of thecompletely diametric gulf between ordinary public readers andthe scientific community.Myc Riggulsford is a science journalist and managing director of The WalnutBureau where he runs an annual programme of science communication andmedia training courses in the UK and beyond for research councils,universities, the European Commission, charities and learned societies. Healso hosts science events for public and teaching audiences includingScience on Stage, UK science festivals, and café scientifique, and iscurrently one of the international judges for the European Science Teacherof the Year awards. Here, from his Devon smallholding, he muses on theimportance of science communication and explains how and why there ismuch to be gained for scientists who indulge.So is neuroscience likely to become as controversial as stem cellresearch or GM foods in the near future? – No, probably not. Butare your future medical advances in our understanding of drugand alcohol addiction, anorexia, Parkinson’s and obesity likelyto be misinterpreted by the public, media and alternative medicalpractitioners? – Yes, very likely.So what can we do to make sure that the public (and fundingbodies, concerned relatives, nurses, government ministers andall the other meddlesome and legitimate tax paying members ofour society) understand the implications of scientific findings soclearly and so accessibly that neuroscience gets the credit andsupport it so obviously deserves and needs?Public mistrust has driven an explosion in scientists’ efforts tocommunicate their work in the last twenty years, along with ahunger from the public, industry and government to understandthem. If we, the taxpayers are, paying for the work, then we havea right to know what is being done in our names.Our physicists, chemists, biologists and other science expertshave had to learn to communicate better if they are not to loseeven more public confidence, faced with outrage and protestfrom pressure groups and the public over health scares, pollutionand personal safety issues. Newspapers, radio and televisionhave also had to find journalists who can understand andinterpret jargon and the highly technical reports which oftencontain vital information affecting our future lives.You might expect that government and industry would resist anyattempts to make the scientists’ work understandable, especiallysince investors and decision makers are a focus of the pressuregroups’ anger. However, British and European politicians andsenior scientists have realised that, if society is to benefit fromnew types of jobs and ways of working using mobile telephones,the internet and all the other modern technologies, and gain thefull benefits which science, technology and medicine can deliverfor society, then people need to understand science better.Which means engaging us in dialogue, not simply telling us afterdecisions have been made.At the same time, businesses and industry have realised that, ifthey want shareholder confidence,5

OPINIONforeign and domestic investment, and the benefits from adoptingnew cleaner technologies, then they too will have to start beingmore open and accountable in their practices. And explain andpublicise the science they are using - especially if they wantpublic confidence and the freedom to operate in a democracy.British (and European) science receives little recognition andsupport compared with American or Japanese research effortsand results. This means our country risks losing its most talentedscientists in a brain drain, many of whom feel they lack funding,jobs and modern technologies through lack of investment, andlack of proper access to useful collaborations, grants, investmentand links with the international research community.In Britain during the last twenty years, science communicationhas developed into an important part of our lives. People areeager to hear about the latest developments, medical advancesand environmental threats. We expect news reports about thelatest science, medicine and technology. And we expect themto be so well written that they are as easily readable as the restof the news. However, this is not as simple as it sounds. Ouropinion makers and leaders in the science community becameaware a few years ago of the mismatch between publicconfidence in science and technology, and the economic andsocial benefits which would be available through better publicunderstanding. The initial reaction of traditionalists was to try to‘educate’ the public by making them understand more science,but in the way that scientists view the world. However, it quicklybecame apparent that this approach does not work effectively,and is not what we the public necessarily want.This top down ‘deficit’ model of communication – based uponscientists’ belief that the public is at fault and should simply knowmore facts - was fairly quickly abandoned by the best sciencecommunicators, and a ‘dialogue’ model was adopted instead.Instead of increasing the volume of teaching science or medicaltechnicalities to the public, efforts are being made in Britain toimprove the quality of communication. Scientists now want opendialogue with the public, exploring our fears and concerns aboutscience and making more of an attempt to help us understandwhy research needs to be done, and how it is relevant to oureveryday lives.In return, doctors and scientists have had to learn bettercommunication skills, use informal channels of communicationsuch as the web, newspapers, radio and television, and bereceptive to public fears, even though these may often appeartrivial or irrelevant. Scientists find the dialogue approach morechallenging as it involves a mental shift from being insiders andhaving specialist knowledge that the public does not share, tobeing partners in a collaboration for the benefit of all our society.Most science in the UK is done using public money, directly orindirectly taken from taxpayers, and scientists must learn to viewthemselves as being responsible to the public for these fundsand for the trust put in them by our public. This requires greatereffort from researchers to make their work accessible andunderstandable to the public, and a responsibility to learn howto make their communication effective. It also means embracingthe idea that research is only truly useful once it is communicatedto a wider audience within the scientific community and to keydecision makers, industry partners and our general society.As scientists’ attitudes have changed and sciencecommunication has become more professional, the debate hasmoved ‘upstream’ in the scientific and technologicaldevelopment process. In some rare cases, this is now allowingthe public to go further than two-way dialogue and actuallyinfluence what research is done. The UK has held public debatesabout controversial technologies such as stem cell research,nanotechnology and GM foods, for instance, in new attempts toimprove relationships between science and society.In Britain, we also have a competitive environment amongstuniversities and research institutes, each striving to gain a shareof the overall science research funds provided by public moneythrough government channels, charities and investment fromindustry. This competitive environment encourages individualscientists, research departments and institutes to issue highquality press releases explaining their successes in science andmedical research and the benefits these will bring to society, sogaining recognition for their expertise and attracting further fundsfor research to their own establishment, as well as the beststudents.The different sectors of UK funding bodies similarly issue theirown high quality press releases about research results. Fromthe public sector, these justify the use of taxpayers’ money andencourage continued political support for research efforts. Fromcharities, they explain what successes have been achieved usingpublicly donated funds and enable fundraisers to continue theirefforts. From industry, they build shareholder confidence andhelp attract further investment. This means hundreds of goodquality press releases arrive daily at newspapers, radio, televisionand online media through conventional post, email and internetwebsites from funding bodies and many individuals. This letsjournalists choose the most interesting stories, most significantadvances and most clearly written press releases as the basisfor their own news stories, which must then compete with othersources of news and topics to make it into the media, makinginteresting news for our readers and listeners.This double competitive pressure means that British science iswell written about and clear, and has recently stimulated thegrowth of a new profession of science communicators and pressofficers within UK academic institutions to act as bridgesbetween scientists and the media or public. It has alsoencouraged the rise of a new specialism within the media of‘science journalism’, people who are experts in understandingand explaining the context and significance of scientificadvances.This treatment of science by experts within the British media hasfurther increased the confidence of doctors and scientists indealing with journalists, and encouraged public discussion ofpreviously difficult concepts such as climate change,nanotechnology, biodiversity or genetic modification. The morethat interesting science appears in the media, the greater theappetite from news media and the public. Once more, we arelearning to trust our scientists because we can now understandwhat they are doing. And we are sometimes allowed to have oursay in what they do next.In the UK, we have clear distinctions between feature stories,comment and analysis, news reports and advertising space.Filling these different parts of a newspaper is the responsibility ofdifferent editorial departments. In other countries, sciencereporting sometimes contains elements of opinion, comment andcommerciality that would be absent from British news coverage.Interestingly, this helps bolster our UK scientists’ internationalreputations for being fair, impartial and honest.Good science communication is a collaboration, not a battlebetween press and academia. Science and environmentaljournalists can help to open the public debates that are vital toa democracy. And researchers find that using the media gainswider recognition for their academic work, which in turn leads tointernational awareness, better research links with otherinternational institutions, and ultimately gets them access togrant funding and collaborations. Oh, and readers get betterstories in their papers.Contact details: The Walnut Bureau, Dadland, HighBickington, Umberleigh, Devon EX37 9BS United Kingdom.Telephone: +44 1769 560268Email: myc@walnutbureau.co.ukNEWSBNA NEWSWelcometo 2007!Richard Dyer, Chief Executive of theBiosciences Federation begins the newyear by describing his concerns about theproposed abolition of peer review panelsand the introduction of a metrics onlybasedRAE.Another New Year has arrived. I hopethat it brings you all the important thingsyou seek and few of those that youdo not.‘The BSF holds the view that it is potentiallydangerous to rely on an algorithm for anactivity as critically important as the RAE. Wethink it essential that there is some wiseevaluation of the quality of the data fed intothe formula.’From a political point, of view I fear thatthe latter will not be true. Thediscussions about the future of the RAEhave now reached a critical point. Themomentum towards the abolition ofpeer review panels and the introductionof a metrics only-based RAE continues.This change is supported strongly bymany of your employers! External toGovernment, the main supporters of themetrics only approach are UniversityVice Chancellors and The Academy ofMedical Sciences. All other“academies”, including The RoyalSociety, The Royal Society ofChemistry, The Institutes of Physics andBiology, and – of course – TheBiosciences Federation are stronglyopposed to the abolition of peer reviewpanels. We want these panelsmaintained and we want them informedby robust metrics including thoserelating to output.The main argument for change is toreduce costs – including those costsassociated with time. We agree thatstrenuous efforts should be made toimplement clear and substantialreductions in the bureaucracyassociated with the RAE and believethat there should be serious discussionabout how can this be achieved. Ametrics only approach will achieve acost reduction but this is not atall the right route to follow. Whydo I write this?First, because the BSF holdsthe view that it is potentiallydangerous to rely on analgorithm for an activity ascritically important as the RAE.We think it essential that thereis some wise evaluation of thequality of the data fed into theformula.Second, because the BSF thinks that ametrics-based formulaic approach willdisadvantage some areas of theBiosciences. We are particularlyconcerned about those importantdisciplines where research is trulyexcellent but grant income is low andoutputs may be relatively sporadic.Research in Systematics is an examplewhere these anxieties are relevant.Third, and following from the previouspoint, the BSF thinks it likely that ViceChancellors will inevitably move tosupport most those areas of theBiosciences most suited to whateveralgorithm that emerges. These areaswill, of course, “do well”.And finally, and personally, because Ihave had too many computer generatedletters from non-existent Bankmanagers based on incorrect informationor a “mistake”. I have alwaysmanaged to receive an apology andcharges reimbursed. I doubt that youwill get (m)any apologies out of the RAE!What can you do about this situation?Well, of course you can continue tosupport the BSF and I would welcomeyour ideas about how costs can bereduced effectively and peer reviewpanels maintained. Some of you couldalso start an interesting discussion withyour employer!There are quite a few issues emergingthat will have an effect on yourprofessional lives. By the time that youread this, I will have met with a TaskForce to discuss the BSF response to apaper published by the ResearchCouncils on Peer Review and ourresponse will be on our web site. If youhaven’t seen the Research Councils’proposals, you might like to downloadwww.rcuk.ac.uk/research/peer/efficiencypr.htm . I don’t wish to prejudge ourresponse to these proposals, but I am100% confident that we will not be100% supportive – and nor will you!I am anticipating a busy year. However,I don’t want all the activity to bereactive. A proactive position, taken atthe right time, can often be moreinfluential than “fire fighting”. Ideally, Ishould like some of the issues where weshould trigger debate to come from theMember Organisations. If you havethoughts about important matters toaddress in the next year or so please letus have them via your Council.We are quite pleased by the number of“hits” our jobs link page received during2006. You may remember that this wasa new initiative for us and is aimed toprovide a resource for postdocs. I write“quite pleased” because we are fullyaware that all web sites can beimproved. If you – or junior colleaguesnot members of the Society – have athought about how improvements couldbe made please contact Dr EmmaSouthern (esouthern.bsf@physoc.org).In fact, please contact us about anybright ideas that you may haveconcerning the BSF. I don’t promise topursue them all, but I do promise to“cherry pick” the very best forconsideration!Dr Richard DyerChief Executive.Biosciences Federationwww.bsf.ac.uk67

NEWS NEWSBNA NEWSBNA NEWSBNA NATIONAL COMMITTEE: NOMINATIONS SOUGHTNominations are now invited for election to the BNA National Committee for TWO vacancies that arise this autumn.Nominees should be proposed and seconded by extant BNA members and sent to the BNA Office(y.allen@bna.org.uk) by 1st JUNE, 2007. Members of the BNA Committee perform a vital role in influencing thegoals and ambitions of this vibrant society. Would you like to contribute for the next three years? Informal enquiriesare very welcome (y.allen@bna.org.uk; tel, 0151 794 5449).This year’s BNA Award for Outstanding Contribution to British Neuroscience went to ProfessorHorace Barlow FRS, a fellow of the Trinity College in Cambridge, for his lifelong contribution to theresearch into the mechanism of visual perception. His pioneering work that studied neuronal activityusing single-cell recordings has been instrumental to our understanding of visual inhibition, theprocess whereby a neuron firing in response to one group of retinal cells can inhibit the firing of anotherneuron, which allows perception of relative contrast. In 1961, he published a seminal article in whichhe addressed the issue of the computational properties of the visual system. This and his subsequentwork have laid the foundations for the burgeoning field of computational neuroscience.The BNA Awards, 2006The BNA Award for Public Service was presented to Mr. Mike Robins in recognition of his tirelesswork in promoting the value of animal research in benefiting human health. “I owe my quality of lifeto this small device,” said Mike Robins, pointing to an electronic controller in his jacket pocket. Heswitched it off and his right hand began to shake violently and uncontrollably. Mr Robins developedParkinson’s disease in his early fifties and, for eight years, his condition worsened until he could nolonger feed or dress himself. Thanks to the successful treatment using deep-brain stimulation, his lifehas changed beyond recognition. “Now I can have a proper conversation, go out on my own, and driveto work,” he said. “Every morning I wake up and marvel that I no longer shake.”Both awards were presented by Professor Richard Frackowiak at The Royal Society in London, on the occasion of the annualChristmas Symposium. This was the last function Richard Frackowiak will undertake for the BNA as he now retires from thepresidency and Graham Collingridge takes up this challenging role.Karen LuytSophie Buglass completed an intercalated degree inNeuroscience last summer at the University of Leeds,deservedly gaining first class honours after an exceptionalperformance in her examinations and thesis. For her finalyear project, she investigated the modulation of calciumhomeostasis by hypoxia and β-amyloid to explore possiblemechanisms of cell death in Alzheimer’s disease. Describedby her supervisor, Chris Peers, as ‘one of the best studentsI’ve had the pleasure to supervise’, Sophie producedpublication-quality data in less than eight weeks. She hasnow returned to her medical course but feels the insightshe has now gained into neuroscience has broadened hercareer prospects immensely such that she might returnto the laboratory bench again one day. She’d bevery welcome!Karen Luyt was also an exceptional student, not averse towinning prizes and medals during her PhD, and publishinga number of papers in quality journals for her outstandingresearch. Supervised by Elek Molnar at the University ofBristol, Karen investigated the cellular and molecularmechanisms of white matter injury in the immature brain,concentrating in particular on the identification and functionof metabrotropic glutamate receptors and GABA receptorsCongratulations to our BNAprize winners for 2006:Sophie Buglass (Undergraduateprize) and Karen Luyt(post-graduate prize), closelyfollowed by runners upHolly Griffiths and Amos Fatokun.in oligodendrocytes, implicated in the cell death,proliferation and differentiation of these cells. Identifyingtheir presence and receptor sub-type might offer thepossibility of pharmacological intervention to mitigate theeffects of premature birth on myelination, Karen hopes.Since returning to her consultant’s position in neonatalmedicine, she feels the experience of her PhD has greatlyenhanced her understanding of white matter developmentand injury in the immature brain, and hopes to seetranslational research directing clinical managementstrategies one day. Her qualifications in both clinicalneonatal medicine and basic neuroscience are anincreasingly essential requirement, she feels, for asuccessful translational approach.So, heartfelt congratulations from the BNA to both Sophieand Karen! But we should also mention two close runnersup:Holly Griffiths, a first class student at the University ofManchester, for the Undergraduate prize; and AmosFatokun, another outstanding PhD student, at theUniversity of Glasgow. Their nominations gave the judgesmuch angst in their decision-making but also muchreassurance in the quality of undergraduate andpostgraduate teaching and research in the UK.Sophie BuglassBNA Committee 2007Professor Graham Collingridge (President)g.l.collingridge@bristol.ac.ukProfessor Colin Ingram (Honorary Secretary)c.d.ingram@ncl.ac.ukDr Stefan Przyborski (Treasurer)stefan.przyborski@durham.ac.ukProfessor Richard Frackowiak (President) rsjf@fil.ion.ucl.ac.ukProfessor Mike Stewart (FENS Rep) m.g.stewart@open.ac.ukDr Duncan Banks (Website Manager) d.banks@open.ac.ukYvonne Allen with Duncan Banks (left) and Peter Woodhams at theBNA stand in Atlanta last year. The BNA exhibits at SfN meetingsevery other year to promote the society on the world stage and say‘hello’ to members, past and present, and to tout for new ones. It isstill a sad fact that many more BNA members go to the Americanmeeting than support their own national meeting, or even the biennialFENS gatherings.In 2005, the Society for Neuroscience decided to change theway it distributed sponsored abstracts to other neurosciencesocieties that may have implications for the future allocation ofthese to BNA members. Although the BNA was one of the firstsocieties to negotiate this ‘deal’ whereby BNA members couldpresent as non-members at the SfN annual meetings, manyother national societies were then also keen to claim a similarallocation. It was fast becoming a chaotic mess so, to simplifythe procedure, SfN decided to give a (still generous) allocationinstead to FENS to distribute to constituent FENS members onits behalf. BNA members still wishing to obtain one of these arenow requested to contact the FENS office directly. However, theFENS Council then decided to impose its own rules andregulations on their distribution, such that priority goes tostudents and early career post-docs only, disproportionately tosmaller societies and to poorer countries. The outcome of thiswas that, although BNA members fulfilling the criteria appear tohave been awarded sponsored abstracts with no problem, thereDr Mike Rigby (Corporate rep) mike_rigby@pfizer.comDr Mike O’Neill (co-opted member) oneill_Michael_j@lilly.comDr Vincent O’Connor V.M.O'Connor@soton.ac.ukDr Andy King andrew.king@physiol.ox.ac.ukDr Narender Ramnani n.ramnani@rhul.ac.ukProfessor Helen Hodges h.hodges@iop.kcl.ac.ukProfessor Judith Pratt j.pratt@strathclyde.ac.ukSecretariat:Dr Yvonne Allen (Executive Secretary): y.allen@bna.org.ukMs Samantha Potts (BNA Administrator): s.potts@bna.org.ukWhere have all the SfNabstract slots gone?was still a proportion of the entire allocation unused.Figure 1:Upon request, the FENS office released the figure (above) todescribe how the ‘slots’ were allocated for the Atlanta meetinglast year. Clearly, BNA members would be wise to still apply(even if they do not necessarily meet all the criteria) and requestto go on a waiting list to receive one of the ‘leftovers’ thistime round.89

NEWS NEWSBNA NEWSBNA NEWSEngaging the public down underThe Manchester Science Group (www.manchesterscience.blogspot.com), comprising lecturers Dr EllenPoliakoff (School of Psychological Sciences, University of Manchester) and Dr Stuart Allan (Faculty of LifeSciences, University of Manchester) and Science Communicators Dr Erinma Ochu and Dr MichelleLockwood, will be running a series of public engagement activities at the IBRO World Congress ofNeuroscience in Melbourne, July 12-17 2007.The group were invited to submit a proposal to the LocalOrganising Committee and this was accepted. Theproposed events build on existing activities developed bythe group over the last couple of years, and include a‘Brain Discovery Stand’ in Federation Square, one ofMelbourne’s foremost public spaces (www.fedsquare.com)The group will also be hosting an interactive pub quiz, ‘YouKnow it Makes Sense’, which has run successfully at CaféScientifique events in Manchester and Nottingham. Aposter will be presented as part of the main congresswhere the group will share with the other delegates theirThe BNA regrets that it must raise the annual subscriptionfee from 1st March, 2007, for all members by a modest£5 per year, to reflect inflationary increases in itsoperational costs over the last year that, in many cases,have risen by nearly 10%. Unfortunately, we now have toask for 10p per week from everyone to help us maintainand improve the service we can offer. This means theannual subscription for full members paying by direct debitwill be £69 per annum, and the student fee will be £35.Please remember that this fee also includes yourmembership subscriptions to FENS, IBRO and theBiosciences Federation that the BNA pays on your behalf– four for the price of one! And some of thesesubscriptions rose by a staggering 200% this year! So,younger members especially should remember to includemembership of all these societies as well on their CVs.The benefits of BNA membership now include:(1) FREE admission to many events throughout the yearincluding ‘One Day Symposia’ and the ever popularChristmas Symposium(2) Reduced registration fees (up to 30%) to theNational MeetingFour for the price of one!ANNUAL GENERAL MEETING 2007The BNA will be holding its Annual General Meeting this year during the19th National Meeting in Harrogate:1.00pm, Tuesday, 3rd April, 2007, Conference Suite, Harrogate International Centre.All members are invited to attendexperiences of developing and delivering public events fordiverse audiences.If any members of the BNA are attending the IBROCongress and are interested in taking part, even for a fewhours, in any of these activities then please contact StuartAllan (stuart.allan@manchester.ac.uk).PLUS – Neuroscientists are invited to participate in ourEuropean Dana Alliance of the Brain DAY IN THE LIFEproject, where scientists give the public an insightinto their lives. Check the blog or email:mansci@googlemail.com for more details.(3) Regular BNA Bulletin and other relevant mailings(4) Regular 'BNA Email Alert' service(5) Student prizes, and bursaries for attendance at BNAand FENS meetings(6) FREE on-line access to European Journal ofNeuroscience(7) Concessionary (SfN membership rate) registrationfees and sponsored abstract forms for Society forNeuroscience annual meeting (now handled byFENS)(8) FREE advertising in the BNA Bulletin and on the BNAWebsite(9) FREE Inclusive membership of the Federation ofEuropean Neuroscience Societies (FENS), theInternational Brain Research Organisation (IBRO) andthe Biosciences Federation (BSF).We do hope you agree that this is tremendous value formoney and that you continue to support as many of ourevents as possible.For further information on any of these benefits, contact:membership@bna.org.ukDrugsfutures – can BNA members help?BNA members with a long (perhapschemically-enhanced) memory mayrecall Drugs Futures 2025, theForesight project on Brain Science,Addiction and Drugs. Set up by thegovernment’s Office of Science andInnovation, it took a 20-year look at thepossibilities for drugs both legal andillegal, for both therapy and pleasure.It reported in 2005, but the story doesnot end there.Instead, the government has asked theAcademy of Medical Sciences to seewhat happens next, and this is wherewe would like your help.The AMS is concentrating on threemain areas of concern about futuredrug use.They are✟ Cognition enhancers.✟ Future legal and illegal recreationaldrugs✟ Drugs for mental healthIt is asking for detailed submissions onthe issues these topics might raiseover the coming 20 years. If you wouldlike to contribute, as an individual or viaan organisation, start by taking alook at the guidelines, which are atwww.acmedsci.ac.uk. The AMS willreport to government by the end of2007.In addition to seeking the opinions ofexperts such as the members of the BNA,the study is also gathering views morewidely.Public engagementJanuary 31 saw the launch, at the DanaCentre in London, of Drugsfutures, aninnovative consultation occurring bothonline and in person. The aim is to getan idea about future developmentsfrom both experts and a wide range ofthe public. Managed by the OPM (Officefor Public Management) with partnersincluding the British Association for theAdvancement of Science, it is runninguntil the end of March.There is a range of ways to getinvolved. One is by invitation only.Defying the insights of Alexei Sayle,who says that nobody should be ableto say they are running a workshopunless they are engaged in lightengineering, we are running someworkshops. They will invite the public(recruited to reflect the olve “thepublic” in the sense of a sample ofindividuals recruited to match thepopulation as a whole) to discuss anddebate the issues. at large. But we willalso be talking to other people who areexperts in some aspect of drug use.They include groups such as youngpeople, drug users, and people whocare for others with mental healthproblems.Each of these groups will be asked toexplore a specific aspect of drug use.They will be helped along the way by abackground note on the futurepossibilities, including a scenario forfuture drug use, that is intended to helptheir thinking without railroading it. Wewill also be inviting some experts to theevents, to provide further information.Each workshop will focus on one ofthese five following themes:• Drugs and the law• Drugs and society• Drugs and young people• Drugs and mental health• Drugs for a smarter brainDuring the workshops, people will bebe asked to explore topics questionssuch as the regulation and control ofdrugs, including the balance betweenregulating addiction via the healthsystem or via criminal justice. Forexample, how far should the use ofcognition enhancers be allowed to go?Should they be illegal for anyone whodoes not have a demonstrable clinicalneed for them? Should they becompulsory for anyone who runs anuclear power station, flies a plane ordrives a bus? What about jobinterviews? If you use a cognitionenhancer to look clever at theinterview, will you feel obliged to take itonce you get the job?A related set of issues will arise whenDrugsfutures considers our emergingknowledge of neuroscience andgenetics. We are starting to findgenuine genetic markets forsusceptibility to addiction, confirmingthe centuries-old wisdom thatdrunkenness runs in the family to adegree that social settings alonecannot explain. At the same time, wemay reach the point of being able to tellwhether an individual expresses genecombinations that make themsusceptible to addiction.One issue we shall explore with thepublic is how to handle knowledgesuch as this. For example, what sort ofcounselling is right for a five-year-oldwith dangerously high levels of drugsusceptibility? He or she mightbecome a problem gambler, a heroinuser, or a heavy smoker, dependingwhat influences they are exposed to.But it is hard to imagine locking themaway from all possible exposure topotential addiction. Almost as tricky isthe advice to give people with a lowsusceptibility to addictive harm. Canthey try any behaviour they like withimpunity?Previous OPM work for the Foresightproject showed that the public is lesspanickedvery able to consider the issuesraised in this project. by the possibilitiesof drug use than one might imagine.They often think that people have a rightto try drugs out, and would be reluctantto have their own children vaccinatedagainst addiction even if it becametechnically feasible.To ensure the sample we need, theworkshops will not be public events.But Drugsfutures has an online life inwhich we hope you will participate, atwww.drugsfutures.org.uk. There youwill find an online consultation whereyou can register painlessly and then letus know what you think.Also at that address you will find theDrugsfutures Blog, where you can joinin discussions of topical issues to dowith addiction and treatment. You willneed to register separately for the blog.We would welcome your comments,questions or suggestions for themes tobe discussed.The team would very much welcomeyour participation in Drugsfutures andwe look forward to your firstcontribution.By Martin InceScience writer and editor of theDrugsfutures BlogDrugsfutures@martinince.com10 11

NEWS NEWSBNA NEWSBNA NEWSThe ECBR, with a current membership of42 scientific institutions from 19 countriesacross the EU, representing 44,000scientists, held its inaugural meeting inBrussels on November 8th 2006. Itelected an Executive Group (Prof. EdithOlah, Chair, Dr Mark Matfield, GeneralSecretary, and three Executive Members,Prof Peter Janssen, Dr. Duncan Banks,and Prof. Christine Giudicelli), andadopted a Manifesto setting out concernsabout the proposed revision of the ECDirective 86/609 which regulates the useof animals in research across EU memberstates. The website (www.ecbr.eu)provides ongoing updates on activitiesand links to member organisations.BackgroundThe ECBR was initiated by EBRAspecifically to coordinate response to therevision of the EC Directive 86/609. Thisrevision was proposed in a report fromthe Environment Committee inDecember 2002, which set up aTechnical Expert Working Group drawnfrom European professional bodies (e.g.EBRA, EFPIA, FELASA), but excludingrepresentative from Patient groups. TheExpert Group planned to draw up areport by the end of 2003, but this wasdelayed for a year by EU elections. ASwiss company, Prognos, was thencommissioned in 2004 to assess theimpact of the proposals, and mounted ahasty preliminary consultation, whichattracted only 66 replies, followedby a long internet questionnairesent to experts, plus requests forviews from the general public. Thequestionnaire/consultation documentprovides a clear indication of what mightbe in the final revision. While the ECBRsupports many of the objectives, thefactual mistakes and the bias of somequestions in the consultation documentprompted the ECBR to draw up itsMembers of the ECBR launch committee:Mary Rice (EBRA), Magda Chlebus (EFPIA), Mark Matfield (EBRA)Manifesto to raise particular concernsand to suggest changes in wording. Theprojected timetable for rolling out theDraft Revision of Directive 86/609include delivery of the final PrognosOpinion in November 2006, inter-serviceconsultation in December 2006, leadingto release of the Draft legislation early in2007, under supportive Germanpresidency of the EU.Adoption of the revised directive willdepend on agreement of the final versionby all three European legislative bodies:the Commission, the Parliament and theCouncil. The rounds of consultationbetween these bodies and theEnvironmental Committee will afford vitalopportunities for ECBR members tolobby and consult with relevantmembers to enhance their understandingof the critical issues involved.Why should the ECBR be concernedabout the revised directive?The ECBR supports legislation toimprove animal welfare and theharmonisation of welfare practice acrossthe EU. However, current evidencesuggests that the revisions may includelegislation which could be detrimental tobiomedical research, without achievingThe Launch ofthe EuropeanCoalition forBiomedicalResearch (ECBR)Members of the ECBR launch committee:Duncan Banks (BNA), Domenico Spina (BPS) and Alan Bateson (BPS)increased welfare benefits, or promotingthe 3Rs. Problematic proposals include:• A ban on first generation bred nonhumanprimates (NHPs)• Extension of cover to someinvertebrates (cephalopods,decapods)• Increased regulation of transgenicanimals and xenotransplantation.• Extension of cover to fetal andembryonic forms• Extension of cover to animals killedfor tissue.Further possible revisions includeprovisions that are effectively in place inseveral EU countries (including the UK),and which the ECBR would seek toclarify and promote:• Compulsory cost/benefit analysis• Ethical review process• Minimum animal/technician ratio• Standardised pain/sufferingassessment• Standardised procedures foranalgesia• Specified methods for euthanasia(ban on CO2)• Implementation of the 3Rs• Regulations for use of animals ineducation and training.Although the details of the draftamendments to Directive 86/609 havenot been released, the ECBR is takingproactive measures:• To alert scientists to the possiblenegative impact of some of theproposals• To inform EU legislative membersabout potential implications in termsof increased costs and administrativeburdens without achievingimprovements in animal welfare.• To suggest amendments to theproposed revisions of Directive86/609 in its ManifestoThe ECBR ManifestoThe Manifesto was finalised at thelaunch meeting and can be seen in fullon the website. The key elementsinclude the following issues:1. Inclusion of ‘recital’ statements toemphasize the• Importance of freedom of researchfor scientific enquiry• Importance of harmonisation ofnational controls on animalexperimentation across EU memberstates2. Euthanasia• All animals to be killed by acompetent person using a humanemethod.• Animals bred for tissue should not beincluded in the scope of the Directive• Ban on the use of CO2 for euthanasiais not justified.3. AuthorisationThe ECBR supports the proposedsystem for authorisation and ethicalreview, but wants time limits andavoidance of duplication in the processto be clearly specified, as follows:• A deadline of 60 days for completionof local and national authorisation, tostart from the date that projects aresubmitted to the local ethical reviewprocess• A statement that the review processmust not duplicate any of the projectassessments made initially by thelocal ethical review body.4. Caging and welfare standardsThe Council of Europe ConventionETS123 has recently revised standardsfor caging and welfare that memberstates must adopt, at an estimated costof over one billion Euros for upgrading.This will cause problems especially foracademic institutions which will needtime to raise funding. The ECBRproposes that the Directive should allow• A minimum of 10 years beforeinstitutions are required to complywith ETS123 standards5. TransparencyThe proposal that all relevant nonconfidentialinformation from theauthorisation process be made publicwould involve huge administrative andlegal costs. The ECBR proposes thattransparency would be more effectivelyand efficiently served by• Publication of a summary of theresearch couched in easilyunderstood language (‘lay summary’)6. Non-Human Primates (NHPs)The proposed ban on use of firstgeneration (F1) purpose-bred NHPs isbased on the erroneous view that mostNHPs are F2. Currently, only New WorldNHPs, constituting 13% of research use,are from F2+ stock. Most EU research(87%) uses F1 Old World NHPs, and F2animals are not available. Welfare wouldbetter served by improving breedingconditions, rather than setting up longtermbreeding colonies, which breedersare not prepared to undertake. TheECBR proposes that• The ban on use of F1 NHPs shouldbe lifted• The EU should set up a system forinspecting NHP suppliers, andapproving their breeding andconservation practices• NHPs should only be obtained fromEU approved suppliers.7. Multiple sitesTo avoid duplication and conflict theECBR proposes that where projects runacross several sites• Ethical approval obtained from anyone institution should be accepted bythe other institutions involvedTrainingIn order to facilitate communicationbetween laboratories and harmonisetraining standards the ECBR proposesthat the directive should charge the ECto set up an Expert Group on training to• Set up training standards andcurricula for EU members• Require member states to adopt andmutually recognise these standardsand curricula.What happens next?The draft Directive is expected to beissued in April 2007. The EC has already(Jan 18) issued a working documentwhich has incorporated several of thesuggestions in the ECBR Manifesto. Thisdocument is confidential, but in generalterms there are still issues to resolve, forexample• Frequency of project reporting toethical review committees• Use of non-human primates• Training requirements• Funding for research on alternativeapproachesTherefore, the ECBR will continue towork to publicise the manifesto, andinform EU administrators and legislatorsabout the issues.The overall strategy involves:• Enlarging the coalition and formingalliances with other interested bodies• Keeping ECBR members and alliesinformed• Targeting MEPs and convincing themto put down amendments whichreflect ECBR proposals• Lobbying MEPs and members of theCommission and Council to supportthese amendmentsWhat can individual ECBR membersdo?Send a message (Fax and email) to yourMEP stating• The problem• The amendment• Arguments for the amendmentThe coordination provided by the ECBRwill be much more effective thanlobbying by individuals or singleassociations. As Mark Matfieldcommented ‘the larger the coalition, themore effective it can be’ Workingtogether we can achieve EU legislationthat will enhance the quality of care forexperimental animals, without imposingundue increases in costs andadministration. Improved welfare willenhance the quality of the sciencethat results.By Duncan Banks and Helen Hodges(d.banks@open.ac.k; h.hodges@kcl.ac.uk)12 13

NEWS NEWSBNA NEWSBNA NEWSThe RDS: Defending the use of animals in research and testingThe use of animals in research has been in thenews frequently in the past year, with thePeople’s Petition earlier in 2006 to the morerecent publication of the Weatherall report inDecember supporting the use of non-humanprimates in research of biological or medicalimportance. Indeed, as neuroscientists, youknow all too well that animals are still necessaryin medical and scientific research and need tobe aware of the arguments in favour and againstas well as the current status of the debate.The Research Defence Society (RDS) is theleading UK organisation that representsdoctors and scientists in the debate concerningexperiments on animals. It recentlycommissioned an opinion poll of GPs thatshowed 96% of family doctors agree thatanimal research has made an importantcontribution to many medical advances. Theresults were announced by Health Minister,Andy Burnham, in October last year.RDS is the only organisation which bringstogether the academic and commercial sectorto work on policy, representation andcommunications. RDS engages in dialoguewith stakeholders, and interacts withlegislators, regulators and government.It has about 5000 members, both individualsand organisations. Members are entitled toadvice, information and assistance on allaspects of animal research, such as dealingwith administrative bodies or the media. Allmembers receive regular information throughpublications and meetings, and may sign up tothe RDS Email News Service. RDS educationalmaterial, produced primarily for schools andcolleges, is also available to members.Most of the activities of the RDS fall into fourcategories: communications, policy andlobbying, information and networking, andsupport for members. It publishes:• a quarterly members’ newsletter, RDSNews, which is essential reading for allthose interested in animal research andanimal rights issues• leaflets and more extensive reports• monitors both media and parliamentarycoverage of relevant issues, as well asanimal rights groups’ publications• provides supporting material to otherorganisationsLast year the RDS set up a Resource Centre tohelp research institutions deal with actual orpotential animal rights extremism and produceda series of good practice guides which givepractical advice to help prevent, prepare for, andminimise the effects of extremism. Morerecently, the Research Centre expanded itsactivities to cover communications, helpingresearch institutions (Universities and Charities)communicate openly and effectively about theuse of animals in research.The annual subscription for full individualmembership is currently £25 per annumpayable by direct debit. A membership form isincluded in this edition of the BNA Bulletin andmay also be downloaded and printed from theRDS web site. (www.rds-net.org.uk).For more information:Corina Hadjiodysseos,Communications Officer, RDSEmail: corinah@rds-net.org.uk;telephone: 020 7478 4333RDS believes that research using animalsshould be well regulated, conductedhumanely and only when there is noalternative. Not all medical research needs touse live animals - useful results are alsoobtained by using computers, studying cellsand tissues, and some studies that are doneon patients and human populations. RDSputs the research processes in context, toexplain when animals need to be used.RDS would like to see a time when animalresearch that causes pain, suffering or lastingharm is no longer required, at least in manyareas of research. However, society hasunmet medical needs and there are gaps inour knowledge. RDS considers that currenttechnical and scientific limitations mean thatfull replacement is unachievable in theforeseeable future.The RDS was founded in 1908 by Dr StephenPaget, at a time of intense public interest inmedical research and animal welfare. Itscomprehensive website contains usefulinformation on animal welfare, the number ofanimals used in research, the types of animaland the research areas in which they areused. The number of animal experiments hashalved over the last 30 years and is nowroughly stable as the increasing use ofgenetically modified animals offsetsreductions in the use of wild-type strains. Thewebsite lists some of the key medical benefitsderived from animal research over the pastcentury and also the benefits for animalsthemselves, mainly through the developmentof vaccines. It also has a recently-introducedhot topics and policy section that addressescurrent issues.Richard Dyer, Chief Executive of theBiosciences Federation, receives an OBEThe British Neuroscience Association would like to congratulate Richard Dyeron the receipt of an OBE in the Queen's New Year Honours List. Richardreceives the award for services to biology, particularly his contribution to theBabraham Institute and Babraham Research Campus.Richard Dyer joined the Babraham Institute in1974 as a neuroendocrinologist, becoming Headof Department in 1985. His distinct scientificcontributions were on understanding howspecialized nerve cells in the brain regulatehormone production and thereby control thefemale reproductive cycle. In 1986, he wasawarded the Annual Medal of the UK Society forEndocrinology and, 1987, the Medal of thePolish Physiological Society. In 1994, he wasappointed Director and led the Institute througha period of great change.In 2005, just before his retirement as Director, theInstitute was highly praised for the excellence ofits research and scientific training in anindependent assessment for the BBSRC, theInstitute’s main sponsoring Research Council.Richard Dyer’s vision of an integrated campus,with researchers from both the academic andcommercial ends of the biotech spectrumworking in close proximity, has been realised.The “Babraham Research Campus”, with itsBioincubator, is now the UK’s most activelocation for start-up and emerging biotechcompanies, with another building due to open inlate 2007 which already has multiple expressionsof interest.Dr Dyer is now Chief Executive of theBiosciences Federation, an umbrellaorganization representing the UK’s biologicalexpertise and providing independent opinion toinform public policy and to promote thebiosciences. He is also Vice President of theEuropean Science Foundation and continues asa member of the Babraham BioscienceTechnologies Ltd. Board.Dr John Bicknell, former Acting Director, said “Iam delighted that Richard’s contribution to theBabraham Institute and to the conception of theBabraham Research Campus has beenrecognized in this way. Richard was the primemover in bringing the Institute to its current, highlyrespected status as a vibrant internationalresearch centre for discovery biology in the 21stcentury with its promise and potential forapplications in biomedicine. This award toRichard is a richly deserved tribute from which hiscolleagues at the Institute will take great pleasure”14 15

NEWSBNA NEWSGenes to Cognition:a neuroscience consortiumfor the scientific communityBNA EVENTSThe Genes to Cognition (G2C) Programme(www.genes2cognition.org) is a systematicintegrative research program that bridgesbasic and clinical neuroscience and wasinitiated by support from the Wellcome Trust.G2C is a consortium of scientists primarilybased in the UK, studying synaptic moleculesand their role in behaviour and disease. TheG2C Programme collects and integrates datain the areas of psychiatry, human and mousepsychology, cellular neurophysiology and cellbiology, proteomics and biochemistry,molecular biology, human and mouse geneticsand genomics.As neuroscientists, we seek to tackle one of thegreat scientific challenges - understanding themechanisms of human behaviour – as well ashelp relieve the enormous burden ofneuropsychiatric disease on our community.Lessons learned from the study of cancer andcell growth have told us that there were farmore molecules, cell biological processes and,ultimately, disease types than ever expected.Importantly, these insights have emerged notfrom one technique or investigator but fromintegrating a diverse range of studies. There isno reason to suppose that the biology of braindiseases will be any less complex.In several areas of biology it is now clear thatlarge scale projects with publicly available dataand distributed resources make an importantcontribution alongside traditional individualprojects and collaborations. Large scaleprojects, through economy of scale, canexpedite progress and remove the need (andcost) for many basic experiments in specialistlaboratories. For example, we no longer needto perform in situ hybridisation to document thebasic expression pattern of genes in the mousebrain because of the Allen Brain Atlas; we nolonger need to manually clone and sequence apiece of genomic DNA from humans, mice andother species because of genome projects.It is very early days for large scale projects inneuroscience. One type of program is where asingle methodology is extensively employed(e.g in situ hybrisidation). Another type ofprogram is where multiple technologies orareas of study are integrated. Systematicprograms that link basic and clinicalneuroscience may be particularly useful to abroad sector of the neuroscience community.G2C scientific strategyThe central theme of the G2C project is thestudy of multiprotein complexes, called NRC(NMDA Receptor Complex) or MASC (MAGUKAssociated Signaling Complex), found atexcitatory synapses in the mammalian brain.These complexes were isolated from mousebrain and found to have a surprisingly largenumber of proteins (~185). Over 50 of thesehave been implicated in human diseases. Inexperimental animal models such as theknockout mouse or drug studies there havebeen ~50 genes reported to alter the propertiesof synaptic plasticity and forms of behaviouralplasticity. These behaviors include learning andmemory, pain, visual and somatosensoryplasticity amongst others. The NRC/MASC setof proteins is clearly very important for humandiseases and animal models of those diseases.G2C scientists are conducting a systematicstudy of mutations and polymorphisms inmouse and human genes encodingpostsynaptic proteins, and exploring how thesegenes influence a broad range of phenotypes -especially cognition.Modular organisation of the consortiumThe consortium has a modular architecturewhere different modules include specificscientific disciplines or activities (see Box 1).Details of people involved with these modulescan be found on the G2C website. Thesemodules provide a natural way for collaboratorsto join the program.The connection between mouse and humangenetics is central to the strategy. In brief, thehuman genetics involves clinical investigatorsinterested in diseases of the brain (e.g.cognitive disorders; mental retardation,schizophrenia, bipolar disorder) and normalcognition (e.g. cognitive ageing and individualdifferences). Human DNA samples aresequenced and analysed for the NRC/MASCgenes and variants identified. Because of theextensive information on these molecules in theG2C program from basic science studies thehuman genetic variants can be rapidlyevaluated. Thus, there are severalcomplementary aspects to the collaborationbetween clinical and basic scientists.The study of the genes in mice typicallyinvolves the generation of knockout mice andexamination of their behaviour (e.g. learningand memory tasks), neurpathology andelectrophysiology studies. The data and allreagents are made available to collaboratorsand widely distributed. One important vehiclefor distribution of data is the G2Cdb.G2Cdb: an integrative databases for synapsebiologyThe G2C program has created an integrativedatabase (G2Cdb) that links multiple databases(see Box 2). We are curating a comprehensivedatabase of all mouse knockouts that havebeen studied in synaptic plasticity. Similarly wehave built a knockout mouse behaviourdatabase. We aim to make these databasesrepositories for published data (curatedmanuscripts), data generated in the G2Cprogram as well as place for data submissiondirectly by external groups. There is a linkeddatabase on the human genetics and diseaseaffecting synaptic proteins. This in turn is linkedto a further database on synapse proteomics.Education and Training in G2CScientific research into the basis of behaviourand disease is of great interest to lay people.We recognise the importance of education onall aspects of the research program and ratherthan develop educational material after theresearch has been completed we aredeveloping that material from the outset. Themajor collaborator in the educational programis the DNA Learning Centre at Cold SpringHarbor (www.DNALC.org). They are developingan education website and materials for schoolsand colleges called ‘G2C Online’. This websitewill contain extensive information, videos andinterviews that informs on all aspects of theG2C research program.Participating in the G2C programThe G2C program welcomes newcollaborators. The interactions, sharing ofinformation and reagents through the programare proving to be very helpful in speedingprogress. Using the modular framework of theprogram provides a simple way to identifyconnections. There are also trainingopportunities for students and scientistswishing to learn new methods. Send anyenquires directly to Seth Grant(sg3@sanger.ac.uk) or through the websitecontact our collaborators.By Seth Grant (email: sg3@sanger.ac.uk)Box 1: Research modulesHuman studies:• Psychiatry & Psychology• Clinical studies• Sample collection• DNA analysisMouse studies:• Creation of mutants• Molecular: RNA and proteomics• Anatomy: Neuropathology• Electrophysiology• BehaviourBox 2: Data resourcesDatabase: G2Cdb• Mouse genetics of synaptic plasticity• Mouse genetics of behaviour• Human genetics of synaptic proteins• Synapse proteomics16 17

BNA EVENTSControversial Issues in NeuroscienceTalkingtherapiesall in the mind?6.30pm for 7.00pm,Wednesday, 27th June, 2007at The Dana Centre165 Queens Gate, London SW7Join us for a lively café – bar discussion between therapists,psychiatrists, psychologists and others to discuss whethertalking therapies can alter the brain as well as the mind.Chaired by Adam Zeman (Professor of Psychology, Exeter).Speakers will include Hanno Koppel (Psychotherapist, Director of DoverCounselling Centre), Chris Brewin (Psychiatrist, KCL) and Brid Hendron(Dentist, hyponotherapist).Tickets are FREE but must be ordered in advance:contact - tickets@danacentre.org.ukThis is part of a series of continuing collaborative events between the European Dana Alliancefor the Brain (EDAB) and the BNAOne Day SymposiumBench to bedside in acute stroke –“Finding our way” or “Lost in Translation”?A timely symposium to review the current status of clinical and preclinical strokeresearch and the current success of translating preclinical research to clinical efficacyWednesday, 17th October, 2007, at The Royal Society EdinburghProgramme• 9.30 to 11.00 Stroke treatments – where are we now?Chair – Richard Morris (Edinburgh)• What treatments are available at present?Gary Ford (Newcastle)• What treatments have been tested, and whyhave they failed?Philip Bath (Nottingham)• 11.30 to 13.00 Stroke treatments – identifyingtherapeutic targetsChair: Charles Warlow (Edinburgh)• A view from industryRichard Green (AstraZeneca)• InflammationNancy Rothwell (Manchester)• Novel Routes to Novel TargetsJames McCulloch (Edinburgh)• 14.00 to 15.30 Bench to Bedside – from laboratory to EDChair: Peter Sandercock (Edinburgh)• The epidemiology of candidate neuroprotective drugsDavid Howells (Melbourne, Australia)• Study quality in preclinical stroke studiesBart van der Worp (Utrecht, The Netherlands)• Does study quality matter?Malcolm Macleod (Edinburgh)• 16.00 Public lectureAnimal models of neurological disease –doing well, getting better?Richard Morris (Edinburgh)Tickets will be FREE for members of the BNA and will include refreshments,lunch and evening reception (non-members, £65; student non-members, £30).For further information and ticket reservations, contact: events@bna.org.uk, or tel: 0151 794 4943/5449.GLIAL CELLSin health and diseaseThe VIIIth European MeetingImperial College, London4th to 8th September, 2007An international meeting that will examine neuron-glial interactions indevelopment, health and disease, and the role of glia in stem cellbiology and regeneration. Imperial College is one of London's largestacademic venues, located in the heart of the museum and culturaldistrict.There will be nine plenaries, twenty-one symposia, lively themedposter sessions, an exhibition and a full range of social events.Dwight Bergels(Maryland, USA)Marie Filbin(New York, USA)Peter Brophy(Edinburgh, UK)Neurotransmitter signalling to oligodendrocytesand neurological diseaseMicroglia: agents of neurodestruction orneuroprotection?Signals from the extracellular matrix in glialdevelopmentCancer stem-like cells in malignant gliomasRepair in CNS demyelinating diseaseGlial migration in the developing andpathological brainWhat can we learn from insect glia?Fate decisions in neural stem and progenitorcellsEpendymal cells and the cerebrospinal fluidPLENARY LECTURERS:Ron McKay(Washington, USA)Helmut Kettenman(Berlin, Germany)Bill Richardson(London, UK)SYMPOSIA:Diverse regulatory roles for gliotransmitters atthe tripartite synapseGlial cells in acute neurological diseases: novelPatrick Charnay(France)approaches to understand pathophysiologyand endogenous glial repair mechanisms.Glial regulation of chronic painFunctional role of Bergmann glia-purkinjecell signallingHow do glial-axonal interactions impact theorganization of the node of ranvier?Neuroinflammation: a two-edged swordTranscriptional control of differentiation inmyelinating cellsGlia in spinal cord injury and regenerationMechanisms of myelinationPierre Magistretti(Lausanne, Switzerland)Linda Watkins(Colorado, USA)Pannexins: an alternative pathway for cell-cellcommunicationThe role of astrocyte dysfunction in epilepsyThe molecular pathology of myelinationABSTRACT DEADLINE: 1st May, 2007Further information: www.eurogliacell.org • Enquiries: Secretariat +44(0) 870 143 6981Organised bythe UK Glial Cell Club, in association with The British Neuroscience Associationwww.eurogliacell.org18 19

SCIENTIFIC REVIEWWe have all heard about migraine. And with more than five millionmigraine sufferers in the UK alone, we probably all know at least afew of them. However, what do we know about migraine as adisease? The answer is probably not very much and this is not inthe least surprising, as, unless we or someone in our householdsuffers migraine, we are unlikely ever to witness the extent of a fullblownmigraine attack. This has, in the past, prevented the broadsocial acceptance of migraine as a severe and very disablingdisorder. In this short review, I shall briefly describe the clinicalfeatures of migraine and highlight recent research on currentlyavailable genetic models of migraine.Clinical Spectrum and EpidemiologyMigraine is an episodic neurovascular disorder that affectsapproximately 6-8% of men and up to 25% of women in the generalWestern population. It is estimated that approximately 12% of thegeneral population have 18 migraine days per year, which poses asubstantial burden on the affected individual and society. Within theEuropean Union, the annual cost associated with migraine exceeds£6 billion. The World Health Organization, therefore, ranks migraineamongst the twenty most-disabling disorders. Since 1988, migrainehas been defined by diagnostic criteria established by theInternational Headache Society 5 and is commonly grouped intomigraine without aura and migraine with aura. As such, a migraineattack can consist of up to three phases: 1) the prodrome, withsymptoms preceding the headache and suffered by about one-thirdof patients; 2) the migraine aura, experienced by about 25-30% ofmigraine sufferers; and 3) the characteristic severe, unilateral (onesided)and often pulsating headache that can last anywhere betweenhours and days.Typical symptoms suffered during the prodromic phase includeretention of fluids, craving for certain types of food and moodchanges. This phase signals the onset of a full-blown migraineattack. Those suffering migraine with aura will experience an aura20Figure 1AFigure 1BRECENT PROGRESS INMIGRAINE RESEARCHSimon Kaja is a Postdoctoral Research Associate in the laboratory ofProfessor Terrance Snutch at the University of British Columbia, Vancouver,having recently obtained his PhD from the University of Leiden. He isinterested in the pathophysiological mechanisms of epilepsy and familialhemiplegic migraine, amongst other things, and his many awards and prizesinclude the BNA’s Undergraduate Award 2002/2003 for his outstandingachievements at Durham University, supervised by Dr Chris Thompson.Here, he describes how genetic models for migraine are enhancing ourunderstanding of the pathophysiology of the disease and have defined amolecular basis for migraine on which to focus research efforts.Figure 1A. Mutations in all three known loci for FHM result in increased levels of theneurotransmitter glutamate, resulting from increased glutamate release from the pre-synapticterminal (FHM1 and FHM3), or reduced clearance of glutamate and K + ions from the synapticcleft by astrocytes (FHM2). As a result, FHM brains are more susceptible to cortical spreadingdepression (CSD), which underlies migraine aura and is a potential migraine trigger(modified from 10 ).Figure 1B. A glutamatergic synapse. The locations of the three known FHM loci are indicated.Cav2.1 channels mediate the calcium influx required for glutamate release; Na + ,K + -ATPases areexpressed in astrocytes and involved in maintaining Na + and K + gradients, required for the activere-uptake of glutamate; Nav1.1 channels mediate the generation of pre-synaptic action potentials.Upward arrows indicate a gain-of-function of the protein (FHM1 and FHM3), the downward arrowa loss-of-function (FHM2). Modified from 9 .phase. The migraine aura is characterised by neurologicalsymptoms, which are typically perceived as visual impairments(seeing dots, flashing lights, or blind spots), but which can alsoinclude speech and movement difficulties or affect sensation. Themigraine headache associated with an attack takes the shape of asevere, unilateral throbbing pain occurring around the eyes andtemples. The headache is accompanied by nausea and increasedsensitivity to light (photophobia) and/or sound (phonophobia).Migraine PathophysiologyThe migraine headache appears to result from the activation of thetrigeminovascular system, consisting of the meningeal andsuperficial cortical blood vessels, which are innervated by thetrigeminal nerve. Projections of the trigeminal nerve through the brainstem (specifically the trigeminal nucleus caudalis) activate higherorder pain centres resulting in headache pain 4 .A series of carefully conducted experiments both in the rodent andhuman brain have led to the now generally accepted hypothesis thatmigraine aura arises directly from a phenomenon termed corticalspreading depression 7 (CSD). CSD is characterised by a slowlypropagating wave of strong neuronal depolarisation across thecortex that is followed by a long-lasting neuronal suppression. OnceCSD reaches the visual cortex, the ensuing neuronal silencing resultsin the characteristic visual aura symptoms.Specific medication for migraine is available. However, only about50% of migraine patients respond satisfactorily to the drugs. Thedesign of effective and prophylactic migraine treatments ishampered by our lack of detailed mechanistic knowledge on howmigraine attacks are initiated. It has been suggested that CSD itselfmay be an initial migraine trigger, and recent animal experimentsindeed provide some evidence for a potential link between CSD andmigraine headache. Specifically, experimentally-induced CSD in ratswas shown to activate the trigeminal system and evoke changes inSCIENTIFIC REVIEWthe meninges and brainstem consistent with the development ofheadache pain 1 . However, direct evidence for such a causativerelationship between CSD and trigeminal activation is still lacking inhumans.Migraine GeneticsMigraine (both with and without aura) shows a strong geneticcomponent and is thought to be of multifactorial origin. However, todate no direct gene involvement could has been shown. It isgenerally assumed that a genetic pre-disposition reduces triggerthresholds for migraine. However, as knowledge of the nature ofmigraine triggers is lacking, research efforts have focussed on asevere and very rare inherited form of migraine: familial hemiplegicmigraine (FHM). FHM is characterised by attacks of migraine withaura, associated with ictal hemiparesis (half-sided body paralysisduring the attack). FHM is generallyconsidered a valid model for the morecommon forms of migraine, especiallysince FHM patients frequently sufferattacks of ‘common’ migraine. Threedistinct genetic loci for FHM have beenidentified to date; all resulting indysfunction at the synaptic level(Figure 1).Mutations in the CACNA1A gene, encoding the alpha-1 subunit ofneuronal Cav2.1 calcium channels, are associated with FHM1 8 .These channels are expressed widely in the nervous system, wherethey are directly involved in the release of neurotransmitter moleculesfrom synaptic nerve terminals. Following an electrical stimulus, thesynaptic membrane depolarises allowing Cav2.1 to open and tomediate an influx of calcium ions into the synapse. These calciumions cause vesicles containing neurotransmitter to fuse with theoutside membrane resulting in the release of neurotransmittermolecules, such as glutamate. FHM1 mutations result in increasedcalcium influx through the mutated Cav2.1 channels, and hence,augmentation of neurotransmitter release.The FHM2 locus is the alpha-2 subunit of Na + K + -ATPase (ATP1A2) 2 .Maintaining a fine homeostatic balance between essential ions (bytransporting Na + out of and K + into the cell), these pump proteinsalso play an important role in astrocyte ion balance that allows forclearing neurotransmitter from the synaptic cleft following its releasefrom the pre-synapse. It is perceivable, how FHM2 mutations thatresult in a loss-of-function of ATP1A2 lead to reduced astrocyticuptake of neurotransmitter.The recently identified FHM3 locus is in the neuronal Nav1.1 sodiumchannel, encoded by SCN1A 3 . Nav1.1 channels are required for thegeneration and propagation of pre-synaptic action potentials,thereby directly influencing likelihood and frequency of neuronalfiring. Those SCN1A mutations identified to date result in anenhanced recovery of Nav1.1 channels from the inactivation thatoccurs after their opening by depolarisation, allowing for a higherfrequency of pre-synaptic action potentials.It appears thus that each of these FHM mutations cause altered ionichomeostasis that ultimately results in increased levels ofneurotransmitter (mostly of the excitatory neurotransmitter glutamate)in the brain; either by the increased release of glutamate (in the casesof FHM1 and FHM3) or by reduced clearance of glutamate byastrocytes in the case of FHM2 (Figure 2).Genetic Migraine ModelsOne of the biggest challenges to migraine research has been theunavailability of sensitised or genetic (animal) models. Recently,however, transgenic knock-in mice have been engineered to carrymutations, originally found in FHM1 patients, in the orthologousmouse Cav2.1 channel.‘Within the European Union, the annual costassociated with migraine exceeds £6 billion. TheWorld Health Organization, therefore, ranksmigraine amongst the twenty most-disablingdisorders.’Knock-in (KI) mice carrying the human CACNA1A R192Q mutation(a single amino-acid change from arginine to glutamine in the Cav2.1channel) do not show any overt neurological or anatomicalphenotype and appear healthy 11 . However, electrophysiologicalrecordings of neurotransmitter release both in the central and theperipheral nervous system showed significantly enhancedneurotransmitter release 6,11 .Cerebellar granule neurones isolated from brains of R192Q KI micehave increased neuronal calcium currents. At the peripheralneuromuscular junction (a synapse almost exclusively dependent onCav2.1 channels for acetylcholine release), R192Q KI mice hadincreased evoked and spontaneous neurotransmitter release underconditions similar to those occurring in the brain during CSD (i.e. lowextracellular Ca 2+ and high K + levels). These changes inneurotransmission have beendemonstrated to be functional,resulting directly from alteredbiophysical properties of the FHM1-mutated Cav2.1 channel rather thanoriginating from e.g. morphologicalabnormalities. Heterozygous FHM1R192Q KI mice show an intermediatesynaptic phenotype in accordance with the autosomal dominantinheritance pattern in humans. Experimental studies in R192Q KImice revealed both a reduced threshold and an increased velocity ofCSD, indicating that Cav2.1 channel mutations can influence theinitiation and propagation of CSD.A second FHM1 KI mouse model (carrying the serine to leucine aminoacid change at position 218) has been generated and is currentlybeing studied. However, no genetic models for either FHM2 or FHM3are available yet. Taken together, FHM1 R192Q KI mice and othertransgenic FHM KI mice can serve as useful models to investigatemigraine pathophysiology and will be instrumental in discoveringmigraine triggers and testing novel therapeutic approaches.Conclusion and OutlookThe identification of FHM-associated mutations in genes encodingtwo ion channels and an ion-transporting ATPase has increased ourunderstanding of the pathophysiology of the disease and defined amolecular basis for migraine, on which to focus research efforts. Afurther boost has come from the generation of genetically sensitisedmouse models. These new genetic models will aid research effortsinto the nature of migraine triggers and the increased sensitivity tothem in migraine patients. These insights will be instrumental fordeveloping in particular novel prophylactic migraine therapies.Acknowledgements:The author wishes to thank Dr. Jaap Plomp and Professor MichelFerrari (Leiden University Medical Centre), Professor Terrance Snutch(The University of British Columbia), Professor Peter Koulen(University of North Texas Health Science Center at Fort Worth) andDr. Christopher Thompson (Durham University) for excellentsupervision and mentoring over the years.Funding for the author’s research on calcium channel mutations wasobtained from Prinses Beatrix Fonds, Hersenstichting Nederland, theKNAW van Leersumfonds, the Michael Smith Foundation for HealthResearch and the Canadian Institutes of Health Research.The author is European Molecular Biology Organization post-doctoralfellow and trainee of the Michael Smith Foundation for HealthResearch.By Simon Kaja (kaja@msl.ubc.caLinks: The Migraine Trust (www.migrainetrust.org)(See page 22 overleaf for references)21

SCIENTIFIC REVIEWSCIENTIFIC REVIEWReferences1. Bolay H, Reuter U, Dunn AK, Huang Z,Boas DA, Moskowitz MA (2002) Intrinsicbrain activity triggers trigeminal meningealafferents in a migraine model. Nat Med8:136-142.2. De Fusco M, Marconi R, Silvestri L,Atorino L, Rampoldi L, Morgante L,Ballabio A, Aridon P, Casari G (2003)Haploinsufficiency of ATP1A2 encoding theNa+/K+ pump alpha2 subunit associatedwith familial hemiplegic migraine type 2.Nat Genet 33:192-196.3. Dichgans M, Freilinger T, Eckstein G,Babini E, Lorenz-Depiereux B, Biskup S,Ferrari MD, Herzog J, Van DenMaagdenberg AM, Pusch M, Strom TM(2005) Mutation in the neuronal voltagegatedsodium channel SCN1A in familialhemiplegic migraine. Lancet 366:371-377.4.Goadsby PJ (2005) Migraine pathophysiology.Headache 45 Suppl 1:S14-S24.5. Headache Classification Committee ofthe International Headache Society (2004)The International Classification ofHeadache Disorders: 2nd edition.Cephalalgia 24 Suppl 1:9-160.6. Kaja S, van de Ven RC, Broos LA,Veldman H, van Dijk JG, Verschuuren JJ,Frants RR, Ferrari MD, Van DenMaagdenberg AM, Plomp JJ (2005) Genedosage-dependent transmitter releasechanges at neuromuscular synapses ofCACNA1A R192Q knockin mice are nonprogressiveand do not lead tomorphological changes or muscleweakness. Neuroscience 135:81-95.7. Lauritzen M (1994) Pathophysiology ofthe migraine aura. The spreadingdepression theory. Brain 117:199-210.8. Ophoff RA, Terwindt GM, Vergouwe MN,van Eijk R, Oefner PJ, Hoffman SM,Lamerdin JE, Mohrenweiser HW, BulmanDE, Ferrari M, Haan J, Lindhout D, vanOmmen GJ, Hofker MH, Ferrari MD, FrantsRR (1996) Familial hemiplegic migraine andepisodic ataxia type-2 are caused bymutations in the Ca2+ channel geneCACNL1A4. Cell 87:543-552.9. Pietrobon D (2005) Migraine: newmolecular mechanisms. Neuroscientist11:373-386.10. Sanchez-del Rio M, Reuter U,Moskowitz MA (2006) New insights intomigraine pathophysiology. Curr OpinNeurol 19:294-298.11. Van Den Maagdenberg AM, PietrobonD, Pizzorusso T, Kaja S, Broos LA, CesettiT, van de Ven RC, Tottene A, van der KJ,Plomp JJ, Frants RR, Ferrari MD (2004) ACacna1a knockin migraine mouse modelwith increased susceptibility to corticalspreading depression. Neuron 41:701-710.Nicotinic acetylcholine receptor signallingand Alzheimer’s Disease: exploring newtargets for therapy Steven Buckingham is a senior research associate at the MRCFunctional Genetics Unit where he has been a regularcollaborator with David Sattelle for many years. He isinterested in invertebrate and human cell-line models ofAlzheimer’s Disease, and uses electrophysiology, calciumimaging and bioinformatics as tools to explore pathophysiologicalmechanisms. Here, he discusses how anunderstanding of the roles of nAChRs in particular, and theirassociated signalling proteins, may assist the discovery of newtargets for the treatment of Alzheimer’s disease.A summary of neuroprotective and Aβ-associateddegenerative pathways at the cholinergic synapticterminal. Activation of α7 nicotinic acetylcholine receptorsby nicotine activates the PI3K/Akt pathway whichprotects neurons from Aβ toxicity. Aβ acts upon nAChRsto activate MAPK/ERK pathways resulting in cell death.Several drugs currently used in the treatment of ADreduce the breakdown of ACh by acetylcholinesterase(AChE), thereby elevating the quantity of ACh available toactivate nAChRs. One of these, galantamine, can also actdirectly on nAChRs to evoke the neuroprotectivepathways. For clarity, α7 nAChRs are shown on thepresynaptic neuron only: although most brain α7 nAChRsare thought to be presynaptic, they can be locatedpostsynaptically at certain synapses. Note that althoughmemantine is known to act primarily through glutamatereceptors, there is also evidence that it also has actionsat ACh receptors.Alzheimer’s Disease (AD) is a debilitating neurodegenerative diseaseinvolving degeneration of predominantly cholinergic neurons,particularly in the basal forebrain inputs to the hippocampus andcortex [46]. The Alzheimer’s Society estimates that dementia currentlyaffects over 750,000 people in the UK, some 55% of which is AD,and by 2010 the problem is likely to be exacerbated with an expected870,000 cases in the UK (http://www.alzheimers.org.uk/News andCampaigns/Policy Watch/demography.htm). However, currenttherapies are of limited effectiveness, and so the discovery of newdrug targets is a matter of urgency. A key step in identifying suchtargets is to develop a clearer understanding of the pathways thatcause neurodegeneration in AD as well as those that protect cellsagainst damage by peptides associated with disease pathology. It isclear that oligomers or aggregates of the β-amyloid peptide (Aβ) playan important role in the development of AD and recent studiesindicate that brain nicotinic acetylcholine receptors (nAChRs) not onlyare affected by Aβ, but also initiate signalling pathways protectiveagainst Aβ toxicity. Thus, understanding the roles of nAChRs andtheir associated signalling proteins may assist the discovery of newtargets for the treatment of AD.Nicotinic acetycholine receptor lossBrain nAChRs are ligand-gated ion channels consisting of fivesubunits that form a central, cation channel which opens in responseto the binding of the neurotransmitter, acetylcholine (ACh). BrainnAChRs are generated from α (α2-10) and β(β2-4) subunits. The 3most important brain receptors are composed of α7, α4β2 andα3β4 subunits. Brain nAChRs have been the subject of studieson the development of AD for the following reasons: 1) the mostvulnerable neurons in AD appear to be those expressing highlevels of nAChRs, particularly those containing the α7 subunit [9];2) the numbers of nAChRs and some of their associated proteinschange in AD; 3) nicotine and acetylcholinesterase (AChE)inhibitors (currently used for treatment for AD) can protectcultured neurons from amyloid toxicity via nAChRs [1, 2]; 4) Aβbinds with high affinity to α7 nAChRs [45]; and 5) polymorphismsof neuronal nAChRs may be linked to AD [43]. It is clear that ADinvolves loss of cholinergic neurons in the brain [11, 31] as well asan overall reduction in nAChRs [32-34] and that different subunitsare differentially up- or down-regulated in AD in a tissue-specificmanner [18], although there are conflicting data on the details ofthe subunit- and tissue-specificity of these changes.Direct actions of Aβ on nAChRsAβ affects nAChRs directly, and most reports indicate that Aβ isan antagonist at nAChRs: for example, Aβ inhibits single channelnicotinic receptor currents in rat hippocampal interneurons [35]as well as α7 receptors heterologously expressed in Xenopusoocytes [17, 36]. However, Aβ activates a mutant (L250T) of theα7 receptor - this mutant conducts current in the desensitizedstate, indicating that Aβ may exert its antagonistic action throughreceptor desensitization [17]. In addition, Aβ action on nAChRsdepends on subunit composition, as it has been reported toblock α7, transiently potentiate α4β2 prior to blocking and haveno action on α3β4 [36].Although most studies report the absence of agonist actions ofAβ, there are some reports of Aβ acting as an agonist at lowconcentrations (1-100 pM) and blocking at higher (nM)concentrations [13]. Similarly, Aβ has been shown to activate α7nAChRs in rat basal forebrain neurons [16] and to cause acalcium responses in presynaptic terminals isolated from rathippocampus and neocortex [15]. Again, despite numerousreports of a block of α7, one study indicated that Aβ failed toblock α7, even though it blocked α4β2α2β2 and α4α5β2receptors [24]. Some of these conflicting reports are likely to ariseeither from differences in the aggregation state of the Aβ used,which is notoriously sensitive to the method of preparation andstorage. In addition, complex interactions with receptorassociatedproteins and/or intracellular signalling pathways thatmodulate nAChRs may account for differences between nativereceptors from different cell types and the various host cells usedfor recombinant receptor expression. Furthermore, although Aβbinds with high affinity to α7 receptors heterologously expressedin Xenopus oocytes [45], indicating that some at least of Aβ’sactions on nAChRs are the result of direct binding to thereceptors, the possibility remains that Aβ actions on nAChRs areindirect, via other functionally-linked proteins.Aβ evokes signalling cascades via nAChRsAβ initiates intracellular signalling cascades via nAChRs,including the MAPK kinase signalling pathway, resulting in celldeath. In hippocampal slices, Aβ activates extracellular signalregulatedkinase (ERK2) isoforms of the ERK mitogen-activatedprotein kinase (MAPK). The sensitivity of this effect to block byα7 nAChR antagonists confirms that Aβ evokes this cascadethrough α7 [14]. Which pathway is activated by Aβ dependsupon the time of exposure to the amyloid peptide: chronicapplications of oligomeric Aβ to hippocampal slice culturesactivate the JNK MAPK pathway but inhibit the ERK MAPKpathway, whereas acute applications of Aβ oligomers do notactivate JNK [4]. In neuroblastoma cells, as well as culturedhippocampal neurons, Aβ activates JNK and ERK and blockingthese stops Aβ hyperphosphorylating tau, as does α7 antisenseoligonucleotides or α7 antagonists, suggesting that Aβ maytrigger tau phosphorylation through ERK and JNK via α7receptors [44].nAChRs mediate neuroprotectionNicotine and its mimetics can protect neurons against Aβ toxicity[23], and α7 receptors play a particularly prominent role innicotine protection. This protective effect is blocked by thenicotinic antagonists, dihydro-β-erythroidine and mecamylamine[22, 41], including the α7-selective antagonist methyllycaconitine[30], indicating that the protective action of nicotine is exertedthrough nAChRs, notably α7. In addition to nicotine, donepezil,rivastigmine (acetylcholinesterase inhibitors currently used astreatments for mild or moderate AD under the brand names ofAricept and Exelon) also protect cultured neuroblastoma cellsfrom the toxic effects of Aβ and this effect is blocked byantagonists of α7, but not of α4β2 receptors [2]. Curiously,although most studies agree that nAChRs need to be activatedfor their protective effects to occur, mouse cortical neurons areprotected by the α7 antagonist methyl lycaconitine [30], raisingthe possibility that neuroprotection by α7 agonists may bethrough desensitization rather than activation of this rapidlydesensitizing receptor. This is of interest and consistent with theα7-dependent activation of intracellular signalling pathways byAβ [4]. Activation of nAChRs also protects against other aspectsof Aβ action: nicotine inhibits free radical accumulation andcalcium dyshomeostasis in cultured hippocampal neurons [28].Nicotinic neuroprotection pathwaysThe PI3K/Akt pathwayThe PI3K/Akt pathway is a well-established anti-apoptoticpathway and has been identified as one important component ofnicotine neuroprotection [22]. The neuroprotective effects ofnicotine are blocked by inhibitors of either PI3K or SRC-familykinases, and nicotine evokes an increase in levels ofphosphorylated Akt, Bcl-2 and Bcl-x [38], which are downstreamin the PI3K/Akt pathway. The protective effects ofacetylcholinesterase inhibitors on neuroblastoma cells isprevented by a blocker of the phosphoinositide 3-kinase (PI3K)-Akt pathway [2]. Janus kinase (JAK2) is another early target inthe nicotine neuroprotection pathway and may mediate signallingbetween the nAChR and the PI3K pathway [37]. Indeed, JAK2may play have a wider role in neuroprotection as it also appearsto be involved in erythropoietin neuroprotection against hypoxicstimuli [12, 40]. JAK2 is also activated by nicotine in nonneuronalcells such as keratinocytes [3].How does activating the PI3K pathway by nAChRs protectneurons? One route is through upregulating the expression ofthe anti-apoptotic protein, Bcl2. The AD therapeutic AChEinhibitors donepezil, galantamine and tacrine increase Bcl2expression when applied to cultured neuronal cells [41].However, nAChR-mediated neuroprotection may also involvepathways other than those regulating apoptosis. For instance,over-expressing PI3K in Drosophila neurons in situ resulted in anincrease in functional synapses as well as synaptic sprouting[29]. So it is possible that nicotine’s neuroprotective pathwaysinclude PI3K upregulation resulting in increased synaptic stability.The pathways linking nAChRs and synaptic stability may providenew drug targets for treating AD.Tyrosine-kinasesMembers of the SRC-family kinases, such as SRC and FYN, arephysically associated with nAChRs [22], but their potential role inAβ toxicity and nicotine protection is unclear. FYN expression isincreased in AD brains, specifically in a subset of neurons with22 23

SCIENTIFIC REVIEWelevated hyperphosphorylated tau protein [39], but it is unclearwhether this increase in FYN contributes to hyperphosphorylationof tau or is a protective response to it. Inextracts of human AD brains, soluble FYN increases withcognitive score and synaptophysin levels and inversely with thetangle count, suggestive of a protective role for FYN [19]. It hasalso been shown that FYN can activate the PI3K/Akt cascade,thereby inhibiting apoptosis [42]. Furthermore, SRC inhibitorsalso prevent nicotinic protection of differentiated PC12 cellsagainst serum-deprivation-induced cell death [26] and inhibitorsof FYN or JAK2 block the neuroprotection against Aβ toxicity oftherapeutic acetylcholinesterase inhibitors [41]. However, FYNmay paradoxically also play a role in Aβ toxicity. Indeed, Aβactivates both FYN and the PI3K cascade [47], while germlineknockout of FYN is neuroprotective in mice [6, 25]. Moreresearch is therefore needed to determine the complex roles ofthis potential therapeutic target in AD and neuroprotection.One receptor, two opposite outcomesHow can nAChRs mediate both the toxic actions of Aβ and theprotective actions of nicotine? Perhaps there is some way inwhich these ligands operate different signalling pathways. Thesimplest explanation might be that Aβ’s antagonist actions blockthe therapeutic effect of nAChR activation. Setting aside thecontroversy over the actions on nAChRs of Aβ, this explanationis unlikely to offer a full explanation because Aβ alone evokesthe ERK/MAPK signalling cascade through α7 nAChRs. Nicotineactivates the ERK pathway but via a different route to Aβ,involving PKA [4]. Thus, α7 receptors appear to be differentiallycoupled to different downstream signalling pathways dependingon which ligand is bound and, in the case of Aβ, on theaggregation state and time of exposure. Further studies arerequired in order to understand more fully how the balance ofsignalling cascades can determine the survival of neurons.References1 Arias, E., et al., Neuropharmacology, 46(2004) 103-114.2 Arias, E., et al., J Pharmacol Exp Ther,315 (2005) 1346-1353.3 Arredondo, J., et al., FASEB Journal, 20(2006) 2093-2101.4 Bell, K.A., et al., Journal ofNeurochemistry, 91 (2004) 349-361.5 Buckingham, S.D., et al., Hum MolGenet, 13 Spec No 2 (2004) R275-88.6 Chin, J., et al., J. Neurosci., 24 (2004)4692-4697.7 Crowther, D.C., et al., Curr OpinPharmacol, 4 (2004) 513-6.8 Culetto, E., et al., Hum Mol Genet, 9(2000) 869-77.9 D'Andrea, M.R., et al., CurrentPharmaceutical Design, 12 (2006) 677-684.10 Dajas-Bailador, F.A., et al., J Neurochem,81 (2002) 606-14.11 Davies, P., et al., The Lancet, 308 (1976)1403.12 Digicaylioglu, M., et al., Nature, 412(2001) 641-647.13 Dineley, K.T., et al., J. Biol. Chem., 277(2002) 25056-25061.14 Dineley, K.T., et al., Journal ofNeuroscience, 21 (2001) 4125-4133.15 Dougherty, J.J., et al., J. Neurosci., 23(2003) 6740-6747.16 Fu, W., et al., J Neurophysiol, 90 (2003)3130-3136.17 Grassi, F., et al., J Physiol (Lond), 547(2003) 147-157.18 Guan, Z.-Z., et al., Journal ofNeurochemistry, 74 (2000) 237-243.19 Ho, G.J., et al., Neurobiology of Aging, 26(2005) 625-635.20 Jones, A.K., et al., Nat Rev Drug Discov,4 (2005) 321-30.21 Jones, I.W., et al., J Mol Neurosci, 30(2006) 83-4.22 Kihara, T., et al., Journal of BiologicalChemistry, 276 (2001) 13541-13546.23 Kihara, T., et al., Brain Research, 792(1998) 331-334.24 Lamb, P.W., et al., J Mol Neurosci, 27(2005) 13-21.25 Lambert, M.P., et al., PNAS, 95 (1998)6448-6453.26 Li, Y., et al., Brain Research, 830 (1999)218-225.27 Link, C.D., Exp Gerontol, 41 (2006) 1007-13.28 Liu, Q., et al., 141 (2004) 746-754.29 Martin-Pena, A., et al., J Neurosci, 26(2006) 10199-208.30 Martin, S.E., et al., Brain Research, 1022(2004) 254-256.31 McGeer, P.L., et al., Neurology, 34 (1984)741-745.32 Nordberg, A., Dementia and GeriatricCognitive Disorders, 8 (1997) 78-84.nAChRs and calcium signallingThe nAChRs may provide a link between Aβ and disruption ofcalcium homeostasis, which is also thought to play a part in AD.The α7 subtype may be of particular relevance since it is muchmore permeable to calcium ions than most nAChRs. Acuteapplication of Aβ to the human neuroblastoma cell line results ina rapid increase in intracellular calcium ions which is dependentupon both α3β2 and α7 nAChRs. This calcium signal arises fromthree sources: influx of extracellular calcium through voltagegatedcalcium channels, release of calcium from intracellularstores, and calcium influx through the α7 receptors. It has beenshown that the α7 receptors, but not the α3β2, specificallytrigger calcium release from intracellular stores by activatingryanodine receptors [10]. Such a specific functional coupling ofα7 receptors and ryanodine-sensitive stores may provideanother site of therapeutic intervention.Conclusion: nAChRs as a route to new therapiesWhile it is clear that Aβ kills neurons and nicotine protects themagainst Aβ toxicity, much remains to be resolved to unravel themechanisms by which death or survival is the outcome.Intracellular signalling initiated by Aβ and nicotine is complex andinvolves much cross talk between diverse signalling pathways,arguing for a systems-based approach to understandingprecisely how nicotine or Aβ can determine a cell’s fate. Such atask could be facilitated by the deployment of mutant suppressorand RNAi screens as well as the ease of transgene production,afforded by invertebrate model genetic organisms [5, 7, 8, 20,27]. Identifying new components of these pathways offers theprospects of new targets for the treatment of AD. In addition,because α7 receptors are present in human lymphocytes, ADrelatedalterations in expression of the receptor and/or keyassociated proteins in these cells may form the basis of abiomarker for early detection of AD or evaluating progression ofthe disease and responsiveness to drugs [21].33 Nordberg, A., et al., Journal of NeuralTransmission - Parkinson's Disease andDementia Section, 2 (1990) 215-224.34 Nordberg, A., et al., Alzheimer Diseaseand Associated Disorders, 9 (1995) 21-27.35 Pettit, D.L., et al., J. Neurosci., 21 (2001)120RC-.36 Pym, L., et al., Br J Pharmacol, 146(2005) 964-971.37 Shaw, S., et al., J. Biol. Chem., 277(2002) 44920-44924.38 Shimohama, S., et al., BiologicalPsychiatry, 49 (2001) 233-239.39 Shirazi, S.K., et al., Neuroreport, 4 (1993)435-7.40 Siren, A.L., et al., Proceedings of theNational Academy of Sciences of theUnited States of America, 98 (2001)4044-4049.41 Takada-Takatori, Y., et al.,Neuropharmacology, 51 (2006) 474-486.42 Tang, X., et al., Cell Death Differ, 14(2006) 368-377.43 Vasto, S., et al., Rejuvenation Res, 9(2006) 107-10.44 Wang, H.-Y., et al., J. Biol. Chem., 278(2003) 31547-31553.45 Wang, H.Y., et al., Journal of BiologicalChemistry, 275 (2000) 5626-5632.46 Whitehouse, P.J., et al., Science, 215(1982) 1237-1239.47 Williamson, R., et al., J. Neurosci., 22(2002) 10-20.SCIENTIFIC WRITING PRIZENationalBrainScienceWritingPrize 2006Winning entriesREBECCA POOLEHave you ever witnessed a crime orwondered how good a witness you wouldbe? If a person pushes past you on yourway home one night and it later becomesapparent they had just committed a crime,would you be able to recall their age,build, hair colour and clothing? Manypeople find themselves a witness to acrime and are called upon to provideevidence which often replies upon theirability to remember tiny details about aperson or event.Most people forget information eithertemporarily, for example when you can’tthink of a particular word, or morepermanently, where details of anexperience are lost over time. However,even when our memories can be recalledwith vivid detail, they are not necessarilyan absolutely true account of whathappened. For example, memories ofsomething we do regularly, like shopping,can become blurred into one genericrecollection. Perhaps more fascinating isthe observation that we can unwittingly fillin gaps in our memory with an imagineddetail and, even if we initially remembercorrectly, our memories can later beoverwritten with new false memories.These observations beg the question, howAs part of our commitment to communicating progress in brain research to a wideraudience, the BNA last summer again joined forces with ‘Your Amazing Brain’website and the European Dana Alliance for the Brain (EDAB) to host anothernational ‘Brain Science Writing Competition’. There were two categories: aresearcher category, open to anyone actively engaged in neuroscience research,from postgraduate students to professors; and a general category, for anyone atall with a passion for writing about science. The brief was to communicatesomething inspiring and informative in maximally 750 words, and in a style thatwould be accessible to all, much like a national newspaper article. The result wasa fascinating array of essays, including a wonderful collection from Year 10 pupilsat Tudor Hall School, Banbury, Oxfordshire. On behalf of the three judges, Dr PennyFidler (Your Amazing Brain website), Dr Yvonne Allen (BNA) and Elaine Snell(EDAB), we hope you enjoy reading the winning entries in each category and acouple of those deemed ‘highly commended’, including one from a sixth former.General Category – 1st PrizeThe truth, the whole truth andnothing but…?reliable are our memories and how easilycan they be manipulated? A questionwhich is of great significance for thevalidity of eyewitness accounts of crimes.Dr. Giuliana Mazzoni, Reader inPsychology at Plymouth University,believes that it is all “too easy” tomanipulate a person’s memory and hasdemonstrated the mere suggestion thatan individual has witnessed orexperienced something can be enough forthem to create a memory of it. Althoughthis research was carried out under strictlycontrolled laboratory conditions there issome suggestion that this can alsohappen in the ‘real world’. In 2002, one ofthe major news stories was of the sniperattacks in Washington DC, where 10people were killed. Eyewitnesses reportedseeing a white van leaving several of thecrime scenes. The perpetrators were latercaught and found to have been using ablue car. It seems that a white van wasseen in the vicinity of one of the firstattacks and the constant reporting of thisby the media is thought to have influencedthe memories of the witnesses to the laterattacks who also ‘remembered’ seeing awhite van fleeing the scene. By expectingto see a white van, the witnesses to thelater sniper attacks had invented amemory to fit in with what they wereprimed to believe might happen.In addition to the media, other witnesses,or even the interviewer taking eyewitnessstatements, can influence memories of anevent as demonstrated by ProfessorMaria Zaragoza of Kent State University,USA. By forcing individuals to make upanswers to questions about scenes theyhad not witnessed, memories of thefictitious events were generated and,during later questioning, recalled andbelieved to be true.Dr Mazzoni’s and Dr Zaragoza’s researchsuggests that during the interview processit would be extremely easy for theinterviewer to impose their beliefs on theinterviewee, either by subtle suggestion,or by inflicting pressure to provideanswers to questions, which could resultin the generation of false memories. Theimplications of which are far reaching. Forexample, if part of an eyewitness’testimony proves to be wrong, their entireaccount could be dismissed, even if theremainder is good. And, worryingly, Dr.Mazzoni believes, “A good interview is arelatively rare phenomenon, still”,What’s most puzzling is how falsememories are recalled as though real andyet no memory exists of the forcedresponses, or even the knowledge thatoriginally you simply couldn’t rememberthat detail. Dr. Mazzoni suggests that this“can be due to the fact that peopleremember the content, but forget thesource of the content”. How many timeshave you recalled a fact, but have beenunable to remember how or why youwould know that piece of information?False memories are further strengthenedby the very act of producing them,resulting in very strong traces that areindistinguishable from real memories.While it seems false memories are virtuallyunavoidable, it is clear that more care shouldbe employed when taking witnessstatements and that, for high profile cases,the potential influence of the media shouldnot be underestimated. If you areunfortunate enough to witness a crime,there is a simple piece of advice - try to writedown what you saw as soon as you can.24 25

SCIENTIFIC WRITING PRIZESources of information: for Interviewvia email with Dr. Mazzoni.Zaragoza, M. et al., 2001. Interviewingwitnesses: Forced confabulation andconfirmatory feedback increase falsememories. Psycological Science 12(6):473-477.Loftus, E. 2003. Our changeablememories. Nature Reviews, 4: 231-234By Rebecca Poole(R.L.Poole@bristol.ac.uk)Rebecca Poole graduated with a degree inBiology from Southampton University in 1999.She stayed at Southampton to study for a PhD.in Plant Pathology and, in 2003, joined theFunctional Cereal Genomics group at BristolUniversity to investigate genetic factors thatinfluence bread making quality in wheat.Rebecca enjoys the challenge of sciencecommunication and currently volunteers for theBristol and Bath branch of the BritishAssociation for the Advancement of Science.General Category – 2nd Prize: Genes for alcohol useturn up in drunk worms and Cheapdate fliesInebriated worms and drunken fliesare helping researchers pick thegenetic locks that drive some of us todrink. At Southampton University,scientists are busy studying thewriggling of worms in alcohol. Theworms in question aren't the familiarearth worms you dig up in the garden,“they are natural soil dwellers likeearth worms”, says Prof Holden-Dye,“but these worms are much smaller.They are only just visible to the nakedeye”. C. elegans are in fact just over 1mm long. Somewhere way back onthe path of evolution, they went theirway and we went ours. Interestinglyfor researchers, however, theseworms behave in much the same wayas any of us after one too many.“What's been previously observed byother scientists is that worms initiallybecome overexcited in alcohol, butthen as the amount of alcoholincreases they get sluggish”, saysProf Holden-Dye. Other researchersare using fruit flies instead of wormsto demonstrate the same effects. Fruitflies positively love a drink it seems,perhaps not that surprisingconsidering their fondness for rottingfruit. Scientists measure howunsteady on its feet a drunken fruit flyis by watching how quickly it tumblesthrough an aptly titled device, the“Inebriometer”. The drunker the fly,the more quickly it emerges out ofthe bottom.So what is it exactly that scientists arehoping to learn by observing drunkworms and flies? “There is evidencethat some worms are better at holdingtheir drink than their others,essentially there is variation as to howquickly they get drunk,” says ProfHolden-Dye,” other worms aren'tgood at building up tolerance to theeffects of alcohol; worms that havebecome tolerant are more resistant tothe effects of alcohol after more thanone exposure”. The same is seen inflies. It has been known for some timethat these two factors, initialsensitivity to alcohol and tolerance,might be linked to the development ofalcohol abuse problems in the generalpopulation. “ This definitely isn't thefull story”, says Prof Holden-Dye, “butthey are obviously important factorsthat we can look at in worms andother organisms like fruit flies and thatmight say something about how wedeal with alcohol. We still don't reallyknow that much about how alcoholacts on our brains”.The Holy Grail is to find genes that aretied up with how the brain is affectedby alcohol and those which may playa part in making some of us morelikely than others to develop adependency problem. The humanbrain is jaw-droppingly complex withbillions of neurones, the specialisedcells that comprise the brain andnervous system, and trillions ofsynapses, the junctions betweenneurones that act as communicationgateways. It performs tasks ofunimaginable complexity in the blinkof eye. Frankly, our brains stick twofingers up at even the mostsophisticated of computers we havetoday. By comparison, C. elegans hasa relatively reserved 302 neurones,BY KATE HOLDEN-DYEeach one of which has already beenexquisitely mapped by scientists.These substantially more simpleorganisms are Nature's gift to those inthe genetics business. In much thesame way as it's advisable to learnyour alphabet before you start on thegreat works of Shakespeare,scientists are starting their search forinteresting genes in worms and flies.So far this approach is proving fruitful.Cheapdate (does what it says on thetin, a Cheapdate fly gets drunk veryquickly) and Hangover are two genesthat have been identified in fruit fliesand numerous others have wriggledtheir way into the spotlight in worms.Excitingly, some of these genes arealso known to be at least partlyresponsible for governing how theseorganisms respond to certain stresses,adding credence to the long held beliefthat stress and drug and addictionbehaviours are linked in all of us. Thehard task now is to pin down exactlywhat these genes and others like themdo, so we can begin to unravel howalcohol really works it magic or wreaksits havoc on our brains.Sources:(primary) Prof. Lindy Holden-Dye Uni.of Southampton (permission obtained).Scholz H. et al (2005) Nature 845-7Moore M.S. et al (1998) Cell 909-12Kate Holden-Dye obtained a BSc inBiochemistry and is now finishing off aPhD at the University of Bristol in theSchool of Medical Sciences. Her PhDfocuses on the stability of an integralmembrane protein.Kate.holden-dye@bristol.ac.ukResearcher Category – 1st Prize: Scientists reveal thatautism and hyperactivity have the same causeANGELICA RONALDAlthough Dustin Hoffman gave one ofthe most famous portrayals of autismin Rainman, his co-star Tom Cruise’shyperactive performance on OprahWinfrey’s sofa more recently may alsobe a good depiction, if recent scienceis to be believed! Amazingly one inthree individuals with autism arehyperactive and inattentive, acondition known as ADHD (attentiondeficit hyperactivity disorder).Perhaps a lead role involving bothautism and ADHD would be tooambitious even for Dustin, but offscreen,autism and ADHD are closelylinked. Both conditions begin inchildhood and are associated withdifferences in the brain. It might be,however, that brain differences do notcause autism or ADHD, but arise as aconsequence of living with autism orADHD. On the other hand, we knowthat genes play a part – but until nowwe didn’t know whether the samegenes cause autism and ADHD.That is why my colleagues and I at theInstitute of Psychiatry carried out astudy on autism and ADHD in over6000 pairs of twins. No study until nowhas had the scope to tackle this issue.TEDS (the Twins Early DevelopmentStudy) included identical twins, whoshare all their genes, and fraternaltwins, who share half their genes.Double troubleWe compared how alike one twin’slevel of autistic behaviours were withthe other twin’s amount of ADHDbehaviours. If the same genes causeboth autism and ADHD it is expectedthat in identical twin pairs, who shareall their genes, the level of autisticbehaviours in one twin and the amountof ADHD symptoms in the other twinwill be the same. Less similaritybetween autistic and ADHD behaviourswould be expected in fraternal twinsbecause they do not share all theirgenes. This is what we found.The results showed that at the geneticlevel, autism and ADHD weren’t sodifferent. It became clear from ourfindings that more than half the genesfor one were also influencing the other.Symptom-specific effectsOf course, it is not that simple. Acomplication is that both autism andADHD consist of several differenttypes of symptoms. Odd socialinteraction, communication problemsand obsessive and repetitivebehaviours are all part of autism, andADHD includes inattentiveness andhyperactivity. Earlier work by our grouphas shown that the different autisticsymptoms are caused by mostlydifferent genes. So as well as justlooking at the overlap between autismand ADHD as a whole, we needed tolook at overlap between the separatesymptoms.In this next stage, we found that it wasthe communication difficulties inautism that were caused by the samegenes as ADHD. In contrast, theobsessive and repetitive behavioursshowed very little overlap with ADHD.As Professor Robert Plomin, a coauthoron the study and the deputydirector of the Social Genetic andDevelopmental Psychiatry centre,commented, ‘It’s startling that thereappears to be greater genetic overlapbetween autistic communicationdifficulties and ADHD than there isgenetic overlap within autism itself’. Inother words, children with autismappear genetically to have much morein common with children withinattention and hyperactivity thanpreviously expected.Back to the BrainWhy is this important? The findings willhelp figure out better treatments forautism and ADHD, through providinga clearer understanding of changesthat occur as a result of these genes. Itis likely that the genes that influenceautism and inattention andhyperactivity will have effects in thebrain. It will be important tounderstand these changes in braindevelopment that may underlie bothconditions. For example, brain areasthought to be affected in autism, suchas those involved in processing socialinformation like faces, might also beinvolved in ADHD.Finally, these findings may change theway we view and study autism andADHD. Autism is five times morecommon in males and recentlyProfessor Simon Baron-Cohen putforward the extreme male brain theory.He says that we can understandautism better if we think of it as anextreme form of male characteristics,such as being good at figuring outsystems and focussing less onempathising. Could we suggest thesame theory might apply to ADHDthen, given that it is also five timesmore common in males?That, says the professor, is ‘animportant question for future research.’By Angelica RonaldAfter completing her undergraduatedegree in Experimental Psychology in2000, Angelica Ronald spent a year inadvertising selling snack food.Yearning for a more academic life, shereturned and did her PhD at the SocialGenetic and Developmental PsychiatryCentre at the Institute of Psychiatry,London, on the causes of children’ssocial development and cognitiveability. Her thesis focused on thecauses of autism spectrum conditions.She is currently working as apostdoctoral researcher on geneticresearch into autism and relatedconditions.Email: a.ronald@iop.kcl.ac.uk26 27

SCIENTIFIC WRITING PRIZEResearcher Category – 2nd PrizeStimulating thebrainSounding either like something from sciencefiction or something rather barbaric, deep brainstimulation (DBS), uses electricity applied directlyto the human brain in order to successfully treatneurological disorders. And recent advances withcomputational modelling could help us tounderstand how it actually works.DBS is extensively used to treat different types ofmovement disorders, most commonly the tremor(a repetitive uncontrollable movement of a bodypart) associated with Parkinson’s disease.Parkinson’s disease is a degenerative disease,and occurs due to the loss of a particular type ofbrain cells which contain a chemical calleddopamine. Dopamine is extremely important inthe part of the brain which controls movement(the motor system), and without it patients maydevelop a tremor, and may eventually becomeunable to initiate movement.Such problems of the motor system are thoughtto occur due to abnormal electrical activity in thebrain. This is because brain cells communicatewith one another using essentially electricalsignals. DBS is able to treat such problems byone or two electrodes being surgically implantedin specific areas of the patient’s brain, and anelectrical current being applied through theseelectrodes. This arrangement is shown in Figure1, where we can see the electrodes implanted,and wires leading to the battery poweredstimulator (a device similar to a pacemaker) whichis implanted in the chest. The electricity injectedduring DBS can then disturb the abnormalelectrical signals in the patient’s brain, and easetheir tremor.At present, one in 500 people suffers fromParkinson’s disease, and every year 10,000people are newly diagnosed with it. Since DBSwas pioneered over a decade ago there havebeen over 35,000 implantations worldwide, andthe estimate is that as many as 80% of people who receive thistreatment will experience a reduction or complete suppression oftheir often disabling symptoms. The decision to allow a patient toundergo this surgery depends on a number of factors, and isusually made only after trying the non-surgical option of drugtreatment to replace the lost dopamine.And yet, although DBS is widely used and successful at achievingtherapeutic benefits, the precise way in which the injectedelectrical current affects the electrical activity of the brain is notfully understood. The difficulty is that although we can produceaccurate images of where the implanted electrode is inside thebrain, as shown in the MRI scan in Figure 2, there is no way thatwe can see or measure exactly how the current spreads in tissue,and how this current is interacting with the brain’s own electricalsignals.Another way to try to understand what exactly is going on in the28BY NADA YOUSIFhuman brain during DBS is to use mathematics.As part of a team at Imperial College London, Iam interfacing the clinical research undertaken bymy colleagues, with the development of 3-dimensional computational models of theimplanted electrode and the surrounding area ofbrain. Simple models, like the one shown inFigure 3, can be used to visualise the electric fieldcreated around the electrode. Thesecomputational models can then be used to studyhow the injected current interacts with thesurrounding brain tissue.The goal is to use mathematical modelling tobetter understand how the current influences thebrain’s activity and predict how to use thisprocedure more effectively. Our recent resultsfrom theoretical models explains the difference inthe electric fields created by two commonly usedstimulation approaches, and therefore can helpdoctors to better target the abnormal activity thatexists as a result of disease. The final challengewill be to use such computer models withinroutine clinical practice in order to predict the bestsettings for the current applied to each individualpatient, as and when they require the intervention.As the use of this procedure spreads to newailments such as epilepsy, depression, andbipolar disorder, the number of patients who maybenefit from this surgical intervention will alsosurely increase. But in order to understand moreabout how the electrical current is achieving theobserved effects, theoretical research hand inhand with clinical research needs to beundertaken.Main sources:Benabid, A-L., et al. Deep Brain Stimulation forParkinson’s Disease. Movement Disorders, 2006Benabid, A-L. Deep Brain Stimulation forParkinson’s Disease. Current Opinion inNeurobiology, 2003Parkinson’s Disease Society information sheet: Deep BrainStimulation. April 2006http://news.bbc.co.uk/1/hi/health/medical_notes/199709.stmhttp://www.medtronic.comhttp://www.tiresias.org/guidelines/parkinsons_disease.htmBy Nada Yousif(nada.yousif@imperial.ac.uk)Nada Yousif graduated from Imperial College in 1998, leaving witha keen interest in the workings of the brain. She went on to studythalamocortical networks, and completed her PhD inComputational Neuroscience at the University of Plymouth. Shereturned to Imperial in 2005 to work on theoretical modelling ofdeep brain stimulation, and is currently in the first year of a 3-yearpost-doctoral fellowship funded by the Medical research Council.Highly Commended – Changing the face of our lives:how our innate interest in faces can change thechoices we makeBY GILLIAN PEPPERFaces are important to people. They arestrongly linked with our sense of identity.Anyone who has been watching the newslately will be aware of the surgical pioneeringwork into full face transplants. These are notwithout risk: patients undergoing transplantswill have to take immunosuppressant drugsthroughout their lives to prevent their bodiesfrom rejecting the new facial tissue.Nevertheless, people unlucky enough tohave suffered facial damage are willing totake the risk. So, why are faces so importantto us?Studies have demonstrated that looking atfaces produces greater brain activity thanlooking at strings of letters or textures.Furthermore, newborn infants appear to paygreater attention to faces than to arbitraryobjects. Such evidence has promptedresearchers to suggest that our interest infaces is innate.If indeed we are predisposed to focus onfaces, it may be for good reason. If we wereunable to identify others as friend or foe, wewould quickly run into trouble. Peoplesuffering from prosopagnosia, the inability torecognise faces, do encounter suchdifficulties. Dr Brad Duchaine of the Instituteof Cognitive Neuroscience explains:“Imagine failing to recognise your boss in theelevator or walking right past your boyfriend.Even worse, imagine picking up the wrongchild at daycare or failing to recognizeyourself in mirrors or photos. These sorts ofincidents occur regularly for people with facerecognition problems, and not surprisinglylead to serious social problems.”So we may be predisposed to pay attentionto faces because this confers a socialadvantage. Indeed it’s possible that facesguide us in deciding whom we can andcannot trust. Research by psychologists inCanada has demonstrated that we are morelikely to trust individuals whose facialfeatures are similar to our own. This ispossibly because we use facial resemblanceas a cue to detect kin and are hardwired tocooperate with family. Furthermore,scientists in New York have found that weare disposed to remember the faces ofindividuals who cheat in “social contract”games - exercises such as borrowing moneyand returning it when promised. Naturally,remembering cheats is important if you wishto avoid them in future. Dr Anthony Little, anevolutionary psychologist and face expertexplains: “We are able to retrieve a hugeamount of information about past deeds andreputation based on only a brief viewing of aknown face - we know who has been nice tous or can help us so we can turn to them, andconversely we know who has cheated us orothers in the past and avoid them.”So faces help us to recognise friends and toavoid cheats, but why else should they beso significant? A growing body of researchdemonstrates the importance of facial cuesin what might be one of the most importantdecisions of our lives – our choice of partner.Evidence suggests that we unconsciouslyuse features such as facial symmetry andmasculinity to judge the quality of potentialmates. For example, a symmetrical face isthought to indicate good health, andtherefore “good genes", which ought to bedesirable in a potential mate if we hope toproduce healthy offspring. There can be aconflict of interests for women however,since masculine characteristics indicategood genes, but more feminine featuresconvey a caring personality – one more likelyto invest in rearing children. Research hasfound that generally, young women prefermen with slightly feminised features, but thatwhen their fertility is at its peak, a masculineface is more attractive.Our innate interest in faces is used byadvertisers to sell products. Research fromthe Center for Consumer Marketing hasshown that a smiling face on an advert canlead consumers to a positive attitudetowards the company using the advert,making them more likely to patronize thecompany and to recommend them to others.Faces really are important. They help us todecide who to trust, with whom to mate,even what products or companies to trust.Those who are unable to recognise facescan suffer for it. Those who have lost theirfaces feel lost without them. Not even facesit seems should be taken at face value.By Gillian Peppergillianpepper@gmail.comGillian has a BSc in Zoology withEvolutionary Psychology from the Universityof Liverpool, where she hopes to return tofurther study in 2007. Since graduating in2005, Gillian has completed a variety ofwork experience projects related to sciencecommunication, including work with theScience Media Centre, BBC FocusGillian Pepper as herself, baby morph, agedmorph and 50% chimpanzee using St AndrewsUniversity Face Transformer.Magazine and Newton’s Apple, and has alsospent four months in India working as avolunteer. She is now one of the UK coordinatorsfor Yearoutindia, a company thatsends volunteers to do charitable work atvarious sites in southern India.29

SCIENTIFIC WRITING PRIZEHighly Commended: The real cause ofobesity: addicted to foodBY FLORA DEVLINTelling obese people to ‘just eat less’ isthe equivalent of advising a chronic heroinaddict to ‘cut down a bit’, say scientists.According to research carried out at NewYork’s Brookhaven National Laboratory,obesity is literally an addiction to food.The findings may offer clues to whycurrent strategies to combat obesity arefailing. The condition is as much apsychological problem as a physical oneand should be treated accordingly,scientists urge.It has previously been shown that drugaddicts and alcoholics have fewerreceptors for dopamine, a neurotransmitterassociated with feelings ofpleasure and satisfaction, than nonaddicts.The Brookhaven team, lead byProfessor Gene Jack Wang, hasdiscovered that obesity causes the samekind of changes in brain chemistry. Theresults imply that obese people consumemore food to stimulate the release of‘pleasure’ endorphins in the brain, just asaddicts feel compelled to take drugs toobtain a ‘high’. If you find this hard tobelieve, think about the feeling when youdevour that first mouthful of chocolate.In the experiment, the brains of 10severely obese people and 10 individualsof normal weight were examined. Thesubjects were injected with a radioactivechemical tag, made to bind to thedopamine receptors. Positron EmissionTomography (PET) was used to pick upthe radioactive signals, the strength ofwhich was proportional to the number ofreceptors. The obese group were found tohave significantly fewer receptors. Thestudy further revealed that there is aninverse relationship between weight andthe number of dopamine receptors. Thatis, the more obese the individual, thefewer their dopamine receptors.The advice given to obese people on theNHS Direct website is “Try not to overeat– listen to your body and stop when you’refull.” However, in an obese person, theremay be an overriding message from thedopamine receptors in the brain saying,“carry on eating!”Whether the observed differences in brainchemistry determine obesity or arecaused by obesity is unclear. "It's possiblethat obese people have fewer dopaminereceptors because their brains are tryingto compensate for having chronically highdopamine levels, which are triggered bychronic overeating,” said Professor Wang.“However, it's also possible that thesepeople have low numbers of dopaminereceptors to begin with, making themmore vulnerable to addictive behavioursincluding compulsive food intake." Thisquestion is a current area of investigation.This research revolutionises our understandingof obesity. The focus needs toswitch away from ‘which diet’ to thequestion of how to tackle food addiction.One possibility is prescribing drugs thatartificially alter dopamine levels. However,these drugs are highly addictive and wouldonly be appropriate when a person’sweight is an immediate risk to their health.A better alternative is exercise. Not onlydoes it have the direct physical effect ofweight-reduction, but it also provides theall-important dopamine high.So what is my point? Stop feeding theever-expanding diet industry and get thenation on a bike!.Sources:Brookhaven National ResearchLaboratory www.bnl.govBy Flora Devlin(floradevlin@hotmail.com)Flora Devlin is a sixth form student at StBedes College, Manchester. She iscurrently studying for AS levels in Maths,Further Maths, Physics and Economics.Last year, she achieved 10 A*’s in herGCSEs. She is hoping to study Economicsor Maths at university, and wants to be acivil servant. Her main hobbies are sportand music. She plays both piano andpercussion to a high level and is a regularteam player at school. She is a keenfollower of the modern music scene,especially local Manchester groups andmusicians.MEETING REPORTS MEETINGactivities, improved careers advice, and recruitment of A levelstudents into relevant professional societies (BPS, BNA).Participants left with a sense of achievement, feeling that thepoints made would be heard and might even make a difference.As Matt Jarvis wrote in the ensuing (and ongoing) emaildiscussions: ‘unquestionably an excellent day, really well plannedand organised. It is also clear that this type of genuinemultidisciplinary dialogue can achieve something very distinctfrom what happens at other conferences’Too little, too late?Despite the enthusiasm, the timing of the meeting was not ideal.The QCA (responsible for curricula) has already issued criteriafor the sciences, and the exam boards are revising the syllabusesfor September 2007. This leaves very little time for ourrecommendations to feed through to the QCA and then to theboards, even though seeds may be sown for the future. Ofparticular concern is the loss of the Psychology Project in thecurrent QCA proposal of four assessment units, all to beexternally examined. The project is a key way for students tolearn about experimental design, data collection and analysis.Class or group investigations will not contribute directly toassessment, and it is difficult to see how exam questions willcompensate for direct hands-on experience of research. It isunlikely that the strong support for projects at the meeting willrescue them in time.Too many sciences?The aim of the meeting was to strengthen the scientific contentof A level Psychology. However, QCA proposes five core areas(cognitive, social, developmental, individual differences, andbiological) each with its own methodologies. This large contenthas two damaging effects. First, different exam boards differ inthe prominence given to each area. While this might offer morecourse choice, the lack of a common knowledge base weakensthe standing of A level Psychology in the universities. There wasa strong perception that Psychology A level students arrivepoorly prepared for a degree course in Psychology. Second, acrammed syllabus reduces the time available for understandingscientific methods and developing transferable skills such ascritical thinking and scientific writing. Course planners shouldthink about how to build core areas around analysis of a few keystudies, rather than offering broad superficial coverage.Should we have a Neuroscience A level?Neuroscience fares badly within Psychology A level courses; thebiological component is mainly confined to stress, motivationand emotion. Teachers considered that students attracted toPsychology might be put off by a larger neuroscience element.However, neuroscience is rapidly advancing and offers a host offlexible, exciting career options. Separate A/AS levelneuroscience courses could have a well-structured and focussedprogramme of direct relevance to understanding science at workor in continuing education. This would offer opportunities thatare not possible within the framework of current A levelPsychology or Biology courses.Ageing Research – the new dynamicsNew Dynamics of Ageing (NDA) Research Programme was launched on 1st November, 2006, at the QueenElizabeth Conference Centre, London. This multi-disciplinary research initiative aims to improve the qualityof life in later years by funding ‘the largest and most ambitious research programme mounted in the UK.’NDA combines the resources of five research councils (ESRC, EPSRC, BBSRC, MRC and AHRC), sixGovernment Departments, and seven charities (linked already into the ‘Funders Forum’ for ageing research).Leading members of the government, research councils and ageing research institutions (including LordSutherland of Houndwood, Royal Commission on Long Term Care of Elderly; Lord Hunt of King’s Heath,Minister for Work and Pensions; Ian Diamond, Chair RCUKEG, CE ESRC; Tom Kirkwood, Director, Institutefor Ageing and Health, Newcastle University; Alan Walker, Director of NDA programme; Michael Lake, Chairof Funders Forum) explained and pledged support for the goals of NDA.MEETING REPORTS MEETINGThe future of A’ Level Psychology – discuss!On the behalf of the BNA, Helen Hodges, Emeritus Professor of Psychology, Institute of Psychiatry, attendedan important workshop on the future of A level Psychology and plans to introduce AS/A2 level Neuroscience,hosted at the National Science Learning Centre, York University Campus, 26th – 27th October, 2006. It wasconvened by Professor John Holman and supported by The Wellcome Trust and The Royal Society.Representatives from teaching, publishing, examination boardsand professional societies converged for a brainstormingmeeting about the future of A level Psychology at the NationalScience learning Centre in York, in October. The NLCS team andspeakers (including Annie Trapp, John Holman, and JeremyAirey) devised stimulating group activities centred on how todeepen scientific understanding within A and AS level courses.30Raj Persaud’s keynote address on motivation illustrated just howto communicate science. The meeting ended with a list ofrecommendations to the Qualifications and Curriculum Authority(QCA) and other stakeholders, which emphasised theimportance of reducing the load of course contents in favour ofexploring scientific methodologies. Our wish list also containedresource banks, a dedicated website for teachers, outreachNDA GoalsNDA aims to change perceptions and experiences of ageingthrough direct engagement with older people. The objectives arethree-pronged and centre on(1) understanding views of ageing (dynamic influences, culturaland individual diversity of experiences)(2) generating new knowledge of ageing processes (bysupporting inter- disciplinary and international research)(3) contributing to the development of policies, practices andproducts to help people achieve an active and independent later life.The stark reality is that as older people survive longer they aresupported by a relatively static or even declining proportion ofyounger people in employment – the upside down populationpyramid. The elderly are therefore often seen as an increasingand unproductive burden. However, older people have a wealthof experience and skills that, with creative management, couldextend and develop their career paths or involvement involuntary work. The NDA is committed to changing negativeperceptions and enabling the elderly to participate fully in workand social activities.‘Life expectancy is increasing at a rate of five hours per day’,Tom Kirkwood explained. However, healthy life expectancy is sixyear less than actual life expectancy, so people in later lifeexperience periods of significantly reduced capacity and poorhealth, rather than enjoying their extra years. The NDA will fosterresearch into ageing processes and factors contributing to themaintenance of good health.NDA first and second round fundingThe NDA initiative has already identified five projects for funding,and The Launch Meeting was treated to an impressive round upof progress to date:• Sara Arber (University of Surrey) has gathered together sixacademic partners in six disciplines for work on optimising thequality of sleep of the elderly in care homes, and will work withfour non-academic partners to develop use of blue light, andinvolve relatives and residents associations.• Ruth Hancock (University of Essex) is engaged in modellingthe needs of old people up to 2030. This comprehensiveproject will recruit government departments (e.g. PensionsPolicy Unit, Census Office), health services, industrial partners31

MEETING REPORTS MEETING REPORTS MEETING REPORTS(e.g. BT), statistical experts, and a host of other sources toprovide a rational, knowledge-based perspective for futurepolicy making.• Diana Kuh (UCL Medical School) is making full use of the UKLife Course cohorts, including the 1921 Lothian cohort, to plotpathways to healthy ageing from molecular to social contexts.• Diana McCann (University of Wales, Newport) is re-directingher expertise in smart clothes for sport to developing‘wearable technology’ for old people: clothes that makepeople feel good, manage moisture, control temperature,protect and insulate, and enablethem to present an attractive andconfident outer face to the world.• Leela Damodaran (University ofLoughborough) is making use of thepervasive influence of IT to developways of ‘adapting support to sustain autonomy’ There is a lot ofhelp online already, for example for shopping and finding outabout local or national services. However, this help is not usedeffectively by the elderly as they lose confidence in coping, forgetPIN numbers, or are impeded by tremor or failing eyesight. TheLougborough proposal will develop solutions for user problems,and build an easy access network for supplying information andcontact details about a range of specialist services.Research on invertebrate organisms has already madeoutstanding contributions to Cellular Neuroscience, providingaccess to uniquely identifiable neurons, sometimes of largediameter, facilitating electrophysiological and biochemicalstudies on neural signaling mechanisms and the integrativephysiology of neural networks.Invertebrate neuroscience has been furtherempowered by the sequencing of the firstanimal genome for the nematodeCaenorhabditis elegans and thedevelopment in that same model organismof gene knockdown by RNA interference.UK-based research, which takesadvantage of inverterbrates, continues tobe strong and 85 neuroscientistsparticipated in a lively one day BNAMeeting (9 lectures and 25 posters) at StJohn's College in Oxford on November8th, 2006, organised by David Sattelle(MRC FGU Oxford), Lindy Holden-Dye(Southampton) and Mark Darlison(Nottingham Trent), in collaboration withSam Potts and Yvonne Allen in the BNAOffice.This meeting demonstrated, yet again, thestrengths of invertebrates as experimentalmodels. They offer easy-to-manipulategenetic tool kits to pinpoint gene functionsunderlying complex behaviours. Having ashort lifespan and generation time,invertebrates such as the worm C. elegans32Future (stage 2) programmes start with funding for a year to formnetworks (national and international) between researchers toestablish a basis for collaborative research which willsubsequently form the platforms for full grant applications.The ‘Silver Revolution’The UK research councils have demonstrated commitment toresearch on ageing. The ESRC’s ‘Growing Older’ programmelaunched in May, 1999, which funded 24 projects was the directforerunner of the NDA initiative, whilst the MRC’s life cycleapproach ensures the needs of ageing receive specific, if morelimited, attention. However, it will takea massive shift in research effort andpublic awareness to push through a‘silver revolution’ through which theelderly can participate fully in allaspects of life, instead of beingmarginalised. The NDA initiative willcertainly work towards achieving an independent and healthylife for the elderly. However, this will crucially depend on the fullinvolvement and participation of the elderly themselves, tocreate and sustain momentum.‘This multi-disciplinary research initiative aimsto improve the quality of life in later years byfunding the largest and most ambitiousresearch programme mounted in the UK’By Helen HodgesEmeritus Professor of PsychologyInstitute of Psychiatry, LondonGenes and Synapses:New insights from studies on InvertebratesONE DAY SYMPOSIUM 8th November, 2006, OxfordMuscle cells of the nematode Caenorhabditiselegans labelled with green fluorescent protein,courtesy of Michael Briese, MRC FunctionalGenetics Department.are readily amenable to forward and reverse genetic screens tocorrelate gene activity with certain behavioural characteristics.Genetic manipulations, such as gene overexpression ordeactivation using knockdown by RNA interference, are relativelysimple and, in the case of C. elegans, have even been performedon a genome-wide scale. Thus, manyaspects of neurobiology, includinggenetics, biochemistry and electrophysiology,can be readily studied ininvertebrates providing an excellent firststep in the study of gene function.Mario de Bono showed how the wormcontinues to be an excellent model forestablishing the neural circuitry involvingforaging behaviour and the important roleplayed by oxygen sensing. Also deployingthe worm, Lindy Holden-Dye reported onnew work showing how neuropeptidesregulate important aspects of behaviour.Work on another important genetic modelorganism, Drosophila melanogaster, waswell represented. Mary O'Connelldescribed RNA editing in the fly nervoussystem and showed how this can addgreatly to functional diversity in voltagegatedand ligand-gated ion channels.Mathias Landgraf showed exquisiteimages depicting dendritic developmentand connectivity in the embryonic flynervous system. Michael O'Sheadescribed a fascinating example of naturalantisense regulation of NOS and its role in memory formation.David Shepherd described one example of what is a growth area,the use of invertebrate models to study aspects of humanneurodegenerative disorders by modelling tauopathies inDrosophila.Andrew Jones and David Sattelle reported on molecular andfunctional diversity in nicotinic acetylcholine receptor genefamilies, taking advantage of the new invertebrate genomescurrently emerging (bee, mosquito, flour beetle as well asadditional fly and nematode genomes). Richard Bainesdescribed exciting work on the regulation of neuronal excitabilityvia Pumilio dependent control of a sodium channel gene. SteveNurrish brought us back to the worm at the end of the daydescribing studies on the regulation of neurotransmitter releaseby GTPases. Finally, Robert Walker, a pioneer in invertebrateneurophysiology and always a passionate advocate of such workThe year 2006 marks the100th anniversary of the firstNobel Prize for Physiology orMedicine, which was sharedby Camillo Golgi and SantiagoRamón y Cajal for their keycontributions to the understandingof the nervoussystem. Golgi discovered a new histological staining method thatallows neurons and their processes to be darkly labelled. By usingthis revolutionary technique, Cajal’s meticulous studies of theentire nervous system led to the Neuron Doctrine, which markedthe birth of modern neuroscience. He famously likened nerve cellsto the “butterflies of the soul” – an insightful conjecture thatmental processes are a result of activity of nerve cells in the brain.The BNA’s annual Christmas symposium was held tocommemorate their outstanding achievements in neuroscience.Jane Qiu reports.The symposium, chaired by Richard Frackowiak of UniversityCollege London, got underway with a presentation by JavierDeFelipe of the Institute of Cajal, Madrid. He gave a historicaloverview of research that led up to Golgi’s and Cajal’sdiscoveries and hypotheses, many of which are still largelyrelevant to neuroscience to this day. In the 1850s, scientistsalready realized that there were many types of cortical neuronsthat are different in their size and morphology. It was thought thatthe network of continuous nerve branches is crucial for thefunction of the nervous system, whereas the cell body servesonly to provide nourishment – a hypothesis called the ReticularTheory. It was not until 1873, when Golgi discovered his“reazione nera” (“black reaction”), was it possible to conductdetailed studies of the nervous system.Cajal discovered this important method in 1887 and made aseries of discoveries in the following few years. In contrast to theReticular Theory, he proposed that axons and dendrites endedfreely without continuity with other nerve cells, and that thein the UK, explored some of the common threads in currentthemes and speculated on some key areas where work oninvertebrates can contribute in the immediate future.It emerged that invertebrates can be used to study not only basicneuronal signalling, but also more complex phenomena thatunderpin behavioural plasticity. A large cohort of other postgraduatestudents attended and we listened to a variety ofexcellent talks, ranging from behavioural through to biochemicalstudies, accompanied by some beautiful images and descriptionsof elegant scientific techniques. This friendly and informal meetingprovided students especially with a great opportunity to network,comparing experimental approaches and sharing our enthusiasm.For this, we thank all the speakers and poster presenters, andabove all, the organisers and the BNA.By Zara Luedtke (Southampton) and Michael Briese (Oxford)Butterflies of the Soul: The BNA Christmas SymposiumThe legacy of Golgi and Cajal: past, present and futureBy Jane Qiu14th December, 2006Royal Society, Londoncurrents flowed “in muchthe same way that electriccurrent crosses a splicebetween two wires” – anembryonic version of thenotion of synaptic cleft,which was discovered in the1950s as a result of theadvances in electronmicroscopy. It was based onSam Potts welcoming delegates.this idea that severalscientists, including Cajal, drew up the first detailed circuitdiagram of the cerebral cortex. This had important implicationfor understanding brain function, as Cajal explained to anaudience in the Croonian Lecture during his first visit to the RoyalSociety in 1894. He also discovered dendritc spines, noting, “Thesurface of [the dendrites of Purkinjie cells] appears covered withthorns and short spines”. His conception of plasticity as well astheories regarding nerve degeneration and regeneration areextremely insightful and are roots of some of the most excitingdiscoveries in neuroscientists today.The following speakers presented their areas of research,highlighting how the scientific insights of Golgi and Cajal havehad a significant impact. Alain Prochiantz, of the École NormaleSupérieure in Paris, focused on the role of a family oftranscription factors called homeoproteins in the spatial andtemporal regulation of neural development. He showed that theexpression of the homeoprotein Pax6 instructs the developmentof the eye in zebrafish, and how a gradient of homeoproteinEngrailed is established along the rostrocaudal axis of the tectum(or the target field of retical projection). This gradient is crucial forestablishing the retino-tectal topography: temporal retinal axonsproject to the tectal regions with low levels of Engrailedexpression; nasal retinal axons have the opposite preference.This is confirmed by in vitro studies which show that Engrailedrepels growth cones – a notion that was put forward by Cajal in33

MEETING REPORTS MEETING1909 – of temporal axons but attracts that of nasal axons. DrProchiantz went on to demonstrate the role of anotherhomeoprotein Otx2 during the critical period of visualdevelopment. He showed that the onset of the critical period inthe binocular visual cortex of mice coincides with the transfer ofOtx2 between neurons from the dorsal thalamic to the visualcortex. This passage is dependent on visual activity andspecifies the timing of the critical period. Manipulating theexpression of Otx2 by gain-of-function or RNA interferenceresults in opening and closure of the critical period, respectively.The third speaker Thomas Klausberger, who holds a position atthe MRC Anatomical Neuropharmacology Unit, Oxford Universityand an honorary position at the Centre for Brain Research inVienna, demonstrated how single neurons contribute to globalactivity in the hippocampus. Although Cajal and hiscontemporaries had noted the myriad of neuronal types withdistinct morphology, the extent of this diversity has not becomefully appreciated until the advances in molecular biology andelectrophysiological recordings. As Dr Klausberger explained,the proper functioning of the cerebral cortex requires neuralnetworks formed by projection neurons and interneurons thatprimarily use the neurotransmitters glutamate and GABArespectively.Interneurons have an important role in modulating cortical outputand plasticity. In the basic hippocampus circuitry, for example,the principle cells are innervated by 14 types of GABAergicneurons, which themselves are innervated by 4 types ofinterneuron-specific cells. Dr Klausberger illustrated theanatomical details of such connections and how variousGABAergic interneurons with distinct firing patterns are involvedin communicating with different parts of the brain. He concludedthat different classes of interneurons evolved because distinctsubcellular domains of the pyramidal cells require differentGABAergic modulation in time and that specialised GABAergiccells transmit information about network rhythm and phase toother brain areas.The discussion on GABAergic neurons was continued by AnnetteDolphin of University College London. She has studied the roleof calcium channels in spontaneous activity of Purkinje cells – asubtype of GABAergic neurons in the cerebellar cortex – and howchannelopathies might contribute to cerebellar ataxia. ProfessorDolphin focused on the α 2 δ subunits of voltage-gated calciumchannels, because loss of expression of α 2 δ-2, which is stronglyrepresented in Purkinje cells, has been associated with cerebellarataxia and epilepsy. Furthermore aberrant expression of α 2 δ-1 isassociated with neuropathic pain. She showed that the α 2 δsubunits can increase current density of calcium channels. Thisis mediated by the metal-ion-dependent adhesion site in the VonWillebrand factor-A domain of the subunits, which is responsiblefor trafficking calcium channels to the plasma membrane.Professor Dolphin went on to demonstrate to the audience thatthe integrity of the α 2 δ subunits is crucial for proper brain function.Mutations in the gene Cacna2d2, such as Cacna2d2 du andCacna2d2 du2J , that encodes the α 2 δ-2 subunits result in the socalledducky mice characterized by spike-wave seizures andcerebellar ataxia. Those mutant mice also have slow degenerationof selective regions in the central nervous system and the animalsdo not survive beyond postnatal day 35. In du/du and du 2J /du 2JPurkinje cells, Professor Dolphin observed a reduction in calciumcurrents as well as in spontaneous and depolarisation-inducedfiring rates compared with their normal counterparts. There arealso abnormalities in dendritic arborisation, in the mutant Purkinjeneurons. These observations have provided insight into themolecular mechanisms whereby mutations in the calcium channelα 2 δ-2 subunits result in cerebellar ataxia.34In the next presentation, Antoine Triller, also of the ÉcoleNormale Supérieure in Paris, discussed surface trafficking ofneurotransmitter receptors between synaptic and extrasynapticmembranes. He explained that the number of neurotransmitterreceptors at synapses, which partly determines synapticstrength, is controlled by dynamic interaction with intracellularscaffold proteins. Most receptors are inserted and removed atnon-synaptic locations, and the process of receptor traffickinginto and out of synapses is regulated during development and byplasticity. New insights into this area of research have beenfacilitated by the advent of semi-conductor quantum dotsbecause these new nanomaterials enable measurements at thesingle-molecule level with high signal-to-noise ratio.Dr Triller showed that the scaffolding protein gephyrin is crucialfor the assembly and the dynamics of receptor clusters in thesynaptic and non-synaptic membranes by connecting thecytoplasmic domains of those receptors to cytoskeletal systems.Manipulation of gephyrin expression has an effect on the lateraldiffusion of neurotransmitter receptors in and out of the synapse.In addition, this dynamic behaviour is regulated by intracellularcalcium concentration and by the cytoskeleton in response tosynaptic activity. Intriguingly, lateral diffusion of neurotransmitterreceptors is also regulated by the length of the spine neck aswell as spine morphology, which in turn vary with plasticprocesses. Dr Triller conjectured that receptor movements in themembranes as a result of neuronal excitability might underlie themechanism of excitation-inhibition homeostasis.The topic of the final talk, presented by Michael Coleman of theBabraham Institute in Cambridge, was axonal degeneration. Onetype of axonal degeneration was first observed by Waller in 1850after nerve fibres of the peripheral nervous system (PNS) weresevered. He noted that “It is particularly with reference to nervousdisease that it will be most desirable to extend theseresearches”, and that the purpose of this degeneration process,which was later coined as Wallerian degeneration, was toprepare for regeneration. In 1913, Cajal published a book titled“Degeneration and Regeneration of the Nervous System”, inwhich he detailed many histological drawings and hishypotheses. Dr Coleman remarked that “there is little to observein fixed, wild-type tissue that Cajal did not already report” and,indeed, many researchers have often ended up “reinventing”his discoveries.However, the development of novel, powerful experimentalapproaches, such as living imaging, new disease models as wellas molecular and genetic tools, has allowed researchers to breaknew grounds, explained Dr Coleman. For example, the slowWallerian degeneration mutant mouse (Wlds), in which thedegeneration process is delayed to 2-3 weeks, has been used toshow that both physical injury and a blockade of axonal transporttrigger a proactive axon death programme. The Wld s gene, whichwas identified using positional cloning, encodes a fusion proteinconsisting of a fragment of UBE4B (ubiquitination factor E4B)and the complete coding region of NMNAT1 (NAD + synthesisingenzyme nicotinamide adenylyltransferase 1). This has beenexplored further using transgenic mouse lines YFP-H and GFP-S, where Wallerian degeneration has now been imaged along3cm lengths of individual PNS axons. The fluorescent proteins inthe neurons of these mice make it possible to "bring the Golgistain to life" and follow in real time movies what happens toaxons as they degenerate. By understanding how variouspathways fit together, it is hoped that novel therapeuticinterventions will be developed for treating axonal disorders.By Jane Qiu, a science writer who divides her life betweenLondon and Beijing (jane@janeqiu.com)BOOKS AND REVIEWSThe volume contains twelvepapers organised into seventopics encompassing:• Neurogenesis (Goldman and Windrem on cell replacementtherapy; Sohur et al. on adult neurogenesis and repair withneural progenitors)• Circuits, axon growth, guidance, regeneration andrearrangements (Pasterkamp and Verhagen on Semaphorinsin axon regeneration; Mueller et al. on repulsive guidancemolecules in adult and embryonic CNS)• Developmental plasticity of axonal connections (Low andCheng on axon pruning)• Neurotrophic factors (Reichardt on neurotrophin-relatedsignalling pathways)• Intrinsic control of axon elongation in the embryo and afterinjury (Filbin on developmental recapitulation to promoteaxonal regeneration; Zhou and Snider on intracellular controlof developmental and regenerative axon growth)• Extrinsic control of axon regeneration after injury (Liu et al. onextracellular regulators of axonal growth in the adult CNS;Meier and Schwab on factors affecting spouting, regenerationand circuit formation in the injured spinal cord)• Plasticity of connections in the adult brain (Cai et al., onplasticity of functional connectivity in the adult spinal cord;Rossignol on plasticity underlying locomotor recovery aftercentral and peripheral lesions in adult mammals)This is a really useful collection of papers on factors affectingaxon extension, although there is a certain amount of overlap(e.g. on inhibitory factors in myelin, extracellular matrix, andrepulsive guidance molecules). There are some helpful figuresand diagrams, for example summarising embryonic and adultaxon guidance (Liu et al.), and developmental vs. regenerativeprocesses (Maier and Schwab). Overall, some important themesemerge, which include factors contributing to and limiting adultneurogenesis, neurotrophin signalling pathways, opposing andcomplementary interactions between Trk and P75 NT receptors.Sohur et al. gave warnings about difficulties in identifyingnewborn cells in brain using single markers plus nestin, but werenevertheless optimistic about the potential for neurogenesis tobe induced and amplified in non-neurogenic regions afterneurotoxic or ischaemic insults (e.g. Nakatomi H et al., Cell 110,439-441, 2002).The papers identified several different levels for potentialtherapeutic interventions to repair or reduce axon degeneration,partly informed by differences between the neonatal andmyelinated brain where axon regeneration is severely limited.Zhou and Snider, for example, argue that distinct signallingpathways mediate developmental as opposed to regenerativeThe Regenerating BrainPhil Trans B, Royal Society (Biological Sciences),Vol. 361, number 1473, 29 September 2006ISSN 0962-8436A Theme issue organised and edited by Geoffrey Cook 1 , James Fawcett 1 , RogerKeynes 1 and Marc Tessier-Lavigne 21 Department of Physiology, Development and Neuroscience, Cambridge University, UK.2 Center for Brain Development, Howard Hughes Medical Institute, San Francisco, USA.axon growth at both cell body gene expression levels and at thegrowth cones which act as local assembly units. Understandingthese differences will help us to intervene more effectively. Filbinoutlined strategies for increasing the permissiveness of the extracellular environment by blocking inhibitors such as Nogo orchondroitin sulphate proteoglycans (CSPGs) by antibodies,peptides, or digestive enzymes (e.g. Bradbury E.J. et al., Nature416, 636-640, 2002), and by blocking intracellular signallingcascades or activating alternative pathways, so that neuronswould fail to recognise inhibitory signals. Relatively little attentionwas given to possibilities for cellular repair by transplanting stem,precursor or progenitor cells. However, Goldman and Windremset out guidelines for impairments which might be usefullyaddressed, which emphasised selective neuronal loss as inParkinson’s disease, circumscribed damage as in spinal cordinjury, or well understood deficits as in lysosomal storage deficitsor demyelinating diseases. However, there is also evidence forstem cell graft efficacy following large non-selective lesions (forexample in rodent models of stroke: Modo M. et al. Stroke 33,2270-2278, 2002), and differential mechanisms for graft repairof selective and non selective lesions would have been aninteresting extension to this discussion. Maier and Schwabpresented a comprehensive overview of sprouting, regenerativeand transplant contributions to spinal cord repair. Emphasis waslaid on combined treatments, but possibly more could have beenmade of evidence for effectiveness of olfactory ensheathinggrafts in SCI (Raisman G. in Neural Transplantation inNeurodegenerative Disease, Wiley, Chichester (NovartisFoundation Symposium 231), 94-109, 2002).Opportunities for maximising recovery of motor functions werestressed in terms of the malleability of circuitry, and functionalrather than strictly anatomical circuits controlling movement (Caiet al). Hence the attempts of previously silent pathways to takeon new functions after injury can be fostered by selectivetraining, including the use of robotic devices, and pharmacologicaltreatments such as quizapine. Rossignol clearlyillustrated improved walking in cats after intensive treadmilltraining, despite spinal lesions.The take-home message from the ‘Regenerating Brain’ isoptimistic. Although regeneration of CNS axons after injury isminimal, there are elements of endogenous plasticity andneurogenesis to exploit, opportunities to engraft stem cells, toaugment neurotrophic activity, and to block inhibitory factors inglial scars and ECM, and to divert cell signals that recognise andengage with inhibitory and apoptotic mechanisms. The challengeof promoting axon regeneration in adult CNS is to integratemolecular, pharmacological and behavioural approaches intobiologically complementary and multifaceted therapies.By Helen HodgesEmeritus Professor, Institute of Psychiatry, London35

NOTICE BOARD NOTICE BOARDNOTICE BOARD NOTICE BOARDConferences at:Wellcome Trust Hinxton Hall CampusSpring, summer and autumn, 2007Microbial Genomes 2007:11 - 14 April 2007Organisers: Julian Parkhill, Siv Andersson,Gordon Dougan, Claire Fraser, Vivek Kapur,Frank Kunst, George Weinstock.Humanising Model Organisms toUnderstand the Pathogenesis of HumanDisease: 1 – 4 May 2007Organisers: Roland Wolf, Nadia Rosenthal,Steve Brown, Riccardo Fodde, RudiBalling, Nick HastieAnimal Biotechnology and itsApplication to Animal and HumanHealth:14 – 16 June 2007Organisers: Helen Sang, Jim Kaufman,Michel Georges.Genomics of Common Diseases:7 – 10 July 2007Organisers: Tim Aitman, David Altshuler,Eddy Rubin, Myles Axton. Keynotespeakers Francis Collins, Leena Peltonen.Molecular Biology of Hearing andDeafness: 11 – 14 July 2007Organisers: Karen Steel, Guy Richardson,Allen Ryan.Interactome Networks:29 Aug – 2 Sept 2007Organisers: Marc Vidal, Ewan Birney,Anne-Claude Gavin.Mouse Molecular Genetics:5 – 9 Sept 2007Organisers: Tony Wynshaw-Boris, BillSkarnes, Hiroyuki Sasaki, KathrynAnderson. (This meeting was previouslyheld between CSHL and Heidelberg, butwill be hosted at Hinxton this year).Evolution of Brain and Behaviour:12 – 16 Sept 2007Organisers: Seth Grant, Nicky Clayton,Svante Paabo.Integrated Approaches to BrainComplexity: 26 – 28 Sept 2007Organisers: Nathaniel Heintz, Seth Grant,Jeffrey Noebels. Includes the Francis CrickLecture on Neuroscience by David Hubel.Pharmacogenomics: 18 – 21 Oct 2007.Organisers: Steve Leeder, MunirPirmohamed, Dick Weinshilboum, RolandWolf.For further information, contact:Dr Deborah CarleyScience Programme Manager / Head of Conference CentreWellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1RQtel: +44 (0)1223 495006 • fax: +44 (0)1223 495141email: d.carley@wtconference.org.ukCheck out the Wellcome Trust Conference Programme at www.wellcome.ac.uk/conferences andThe Wellcome Trust Conference Centre at www.wtconference.org.ukInaugural InternationalConference on Advancesin CerebrovascularDiseaseManchester, 5-7 July, 2007Main topicsArterial remodelling in atherosclerosis ● Molecularmarkers of stroke development ● Angiogenesis incerebrovascular disease ● Neuroprotectivestrategies after stroke ● Brain degenerative disease● Gene therapy in treatment of cerebrovasculardiseaseFurther information: www.rihsc.mmu.ac.ukAutism Research in the UK - from diagnosis to interventionNATIONAL CONFERENCE, MAY 11-12 2007, OPEN UNIVERSITY, MILTON KEYNESA two-day meeting to be hosted by the Open University (Biological Sciences Department)Session themesDiagnosis and assessmentEpidemiology and geneticsPhysiological and biochemicalperspectivesNeurology, imaging and brainpathologyPsychological perspectives, languageand communicationManagement and early interventionConfirmed Keynote Speakersand ChairsAnn le Couteur, Tony Charman, JeanGolding, Anthony Bailey, PatrickBolton, Sabine Bahn, Gordon Bell,Declan Murphy, Martin Bax, ElainePerry, Christoph Schmitz, KatePlaisted, Emma Weisblatt, PeterHobson, Jill Boucher, Ayla Humphrey,Dermot Bowler, Jonathan Green, RitaJordan, Patricia Howlin, Anne O’Hare,Anthony Monaco, Peter Mitchell, IlonaRoth, Colwyn Trevarthen, SteveSwithenby, Gavin Malloch, JohnWilliams, Richard Mills, JennyLongmore, Dame Stephanie ShirleySponsors includeMedical Research Council, TheWellcome Trust, Autism Speaks, BritishNeuropathological Society, AutismUnravelledFor further details of the conference,including registration, abstractsubmission and bookings foraccommodation, contact:www.open.ac.uk/ARUK2007.ARUK Conference AdministrationNational Conference on AutismResearch, 2007The Open University (Dept. BiologicalSciences)Faculty of Science, Walton Hall,Milton Keynes, MK7 6AAARUK2007@open.ac.ukVACANCIES VACANCIESJOBSJOBSJOBSJOBSJOBSRoyal College of Surgeons Ireland, DublinCentre for Human ProteomicsPost-Doctoral ResearcherProtein-Interaction Mapping and Neuronal NF-kappaB/ Survival SignallingThe Centre for Human Proteomics (CHP) applies proteomics technologies to identify proteins, their modifications and their role in diseaseprogression. We employ mass-spectometry, fluorescence resonance energy transfer imaging, and protein array technologies for theidentification of protein-protein interactions involved in diverse biological processes such as receptor signalling, survival signalling andapoptosis.We are seeking an ambitious post-doctoral researcher to elucidate protein interactions of IKKs and the NF-kappaB inhibitor IkappaBalphain neurons, using protein array technologies (http://chp.rcsi.ie/) and proteomics approaches. We have recently provided evidence for aselective enrichment of phosphorylated IkappaBalpha and IKKbeta in the axon initial segement of neurons, and their release upon injury.The successful candidate will learn to use present protein array technology for the identification of protein interactions and will be expectedto examine the molecular role of these interactions in neurons.The applicant should have a Ph.D. in molecular biology or a related field and be confident with basic techniques in molecular biologyand protein biochemistry. This post is particularly suited for individuals with an interest in signal transduction and neuroscience.Practical experience with proteomics, neuroscience or analysis of array data are advantageous, but not required. Enquiries and/orapplications (a letter of interest, a CV and a list of up to three referees) should be sent to Prof. Jochen Prehn (prehn@rcsi.ie).Prof. Jochen PrehnCentre for Human ProteomicsRoyal College of Surgeons in Ireland, 121 St. Stephens Green, Dublin 2NYU Medical Center, New York, USAPostdoctoral Research Fellowship in Cortical Electrophysiology and GeneticsThe Fishell lab is looking to hire an experienced electrophysiologist to work on an ongoing project investigating the genetic determination ofcortical interneurons. Ideally candidates should have 2-3 years experience of whole cell patch clamp and be capable of working in a semiindependentmanner. The successful applicant will be responsible for defining the direction of the electrophysiology research but will work inclose collaboration with other members of the lab experienced in developmental genetics. There will also be the opportunity to gain experiencein genetic methods.Informal inquiries are welcome. A full CV and letters of recommendation should be sent to Prof. Gord Fishell at the following email address:fishell@saturn.med.nyu.eduLab website: http://saturn.med.nyu.edu/research/dg/fishelllab/Smilow Neuroscience Program, NYU Medical Center, New York, NY10016, USA.Closing date: until position is filled.3637

VACANCIES VACANCIESJOBSJOBSJOBSJOBSJOBSVoluntary Services OverseasVSO is an international development charity that works through volunteers. Our vision is a world without poverty in which peoplework together to fulfill their potential. We bring people together to share skills, creativity and learning to build a fairer world. VSOwelcomes volunteers from an ever increasing range of countries, backgrounds and ages. National agencies in Canada, Kenya, theNetherlands, the Philippines and India recruit volunteers from many different countries worldwide. This international approach allowsus to combine and learn from a rich variety of perspectives. In all the countries where we work, VSO is represented by a ProgrammeOffice. Staff and volunteers in our Programme Offices work together with local partner agencies, and increasingly with the peoplewhose interests VSO aims to serve, to agree a programme of development priorities in their country and region.Financial supportWe cover all the costs for you. Our financial package for volunteers includes: Salary, return flight , accommodation, medical andtravel insurance cover, national insurance contributions, pension contributions, visas and work permits grants and guarenteed holidays.For information on how to apply go to http://www.vso.org.uk/volunteering/stepthree and complete our online applicationform or call us 020 8780 7500 or email: enquiry@vso.org.uk for more details.You must be living in an EU country to apply for these positions. Please specify your interest in this particular job when youapply and add the reference code to your application form.University of Edinburgh, Doctoral Training CentrePhD studentship: 4 YEAR PhD IN NEUROINFORMATICS and COMPUTATIONAL NEUROSCIENCEThis is a 4 year programme with a strongly interdisciplinary character and is ideal for students who want to apply their computationaland analytical skills to problems in neuroscience and related fields. The first year consists of courses in neuroscience and informatics,as well as projects based in experimental labs. The first year is followed by a 3 year PhD project. The PhD project is commonly donein collaboration with one of the many departments and institutes affiliated with the DTC.The DTC programme is made up of 3 themes:1) Computational and Cognitive Neuroscience.Computational, mathematical, and experimental studies of information processing in the nervous system.2) Neuromorphic Engineering and Robotics.Artificial sensor perception, neuromorphic modelling, spiking computation, and neurorobotics.3) Data Analysis and Systems.Imaging data analysis using machine learning, Bayesian methods, and neurally inspired software.Edinburgh has a strong research community in these areas and leads the UK in creating a coherent programme in neuroinformatics.Edinburgh has been voted as 'best place to live in Britain', and has many exciting cultural and student activities.Students with a strong background in either computer science, mathematics, physics or engineering are particularly welcome toapply. Motivated students with other backgrounds will also be considered.About 8 full studentships are available to UK students and a small number of EU students.The stipend is about 12,300 GB pounds per annum.Applicants from outside the EU will need to provide their own funding and evidence thereof.Full info and application forms can be obtained from:http://www.anc.ed.ac.uk/neuroinformatics. • E-mail: neuroinformatics-phd@inf.ed.ac.ukContact: Mrs Pat Ferguson • Phone: (44) 131 650 3090 • Fax: (44) 131 650 6899Address: School of Informatics, 5 Forrest Hill, Edinburgh, EH1 2QL. Scotland, UKApplications received by March 30th, 2007 will receive priority treatment.38University of Glasgow, Division of Clinical NeurosciencePhD studentshipMRC funded studentship in pre-clinical imaging in neuroscience (4 years)Stroke is a major killer and can cause significant disability in survivors. Specific treatment options are currently limited (thrombolysiswithin 3 hours or aspirin). The time window for acute neuroprotection therapy depends on the length of time injured but potentiallysalvageable tissue (penumbra) survives in each patient. Magnetic Resonance Imaging (MRI) techniques improve diagnostic accuracy,and offer the opportunity for physiological brain maging. This project will involve the development and validation of a new MRItechnique to identify penumbral tissue in the ischaemic brain using established rodent stroke models, imaged in a state-of-the-art7T small animal MR scanner.The 4 year MRC funded PhD studentship, will be available from 1st October 2007 with a stipend of £12,300 per annum. Applicantsshould hold or expect to gain a first or upper second class honours degree in a biological or biomedical science or related field.Eligibility requirements for MRC studentships are listed in the Studentship guide -(http://www.mrc.ac.uk/Careers/Studentships/Informationforstudents/index.htm)For further information contact Professor I Mhairi Macrae (m.macrae@udcf.gla.ac.uk) Tel 0141 330 6978, Division of ClinicalNeuroscience, Wellcome Surgical Institute, Garscube Estate, Glasgow G61 1QH, UK.Applicants should submit a CV including e-mail addresses of 2 referees.A closing date has not yet been set. Applications received by March 30th, 2007 will receive priority treatment.