a newsletter for members of the BNA - British Neuroscience ...

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a newsletter for members of the BNA - British Neuroscience ...

ulletin

I N S I D E

a newsletter for members of the BNA

Secretary’s Report 3 Interview 4 Opinion 5 BNA News 6-8 BNA Events 9-11

Scientific Reviews 12-15 Science and Communication 16-18 Science and the Media 19

Meeting Reports 20-28 Noticeboard 31-32 Vacancies 32-34

Spring 2005 ● Issue 50


Bulletin

SECRETARY’S REPORT

● The BNA is always on the look out for new blood. The committee has

been discussing ways in which we might increase our membership. It

seems that in some areas of the UK we are not recruiting as many

neuroscientists as we could be. As of February 2005, our membership

stands at 1363 full members, 519 students, and 113 who are still ‘lost’.

This is a healthy state of affairs but there are clearly people out there

who we have not reached yet. I don’t have to convince you, as

members, of the benefits BNA membership can bring. However, the

committee would ask that everyone expound BNA membership to

colleagues, particularly new postdocs and postgrads who have not yet

joined our society. It’s worth reminding them that BNA membership

entitles them to abstract forms for the American Society for

Neuroscience meetings amongst a whole range of other things

including reduced registration at our National Meetings and Symposia.

BNA membership fees are very modest and at £20 for student

membership perhaps supervisors could consider gifting membership

as a "hook" to their first year PhD students?

● New blood is also needed on the BNA committee as we have one

vacancy for a nominated member to be filled later this summer. So, if

you feel you want to contribute to BNA activities and/or you would like

some representation of your particular research interest at committee

level, then please consider standing. Elected committee members

serve for three years starting in October and there are four meetings per

annum – not an onerous commitment for such an important activity!

As this newsletter goes out, many BNA members will be involved in

Brain Awareness Week (14-20 March). This international effort is

promoted by the Dana Alliance for Brain Initiatives (DABI). In previous

years, BNA members have taken a leading role in organising events

around the UK to engage the public and to bring brain science into the

public eye. The support for Brain Awareness Week by BNA members

goes from strength to strength every year. Speaking from personal

experience, I can understand why, as being involved in one of these

events is great fun and very rewarding. If you are not involved this year,

why not give it a go next year? And, if you are organising an event this

year, we would be keen to have a report on how it went for publication

in the next newsletter.

● Of course the big event for BNA this year is our National Meeting in

Brighton, April 3-6, 2005. Running a meeting of this size and scope is

a costly business. However, for a meeting with such a strong and varied

programme, and in the delightful surroundings of Brighton, it’s great

value and is still heavily subsidised for all, especially for students.

● An important source of financial support for the meeting comes from

our varied sponsors, such as GSK, Lilly, EDAB, DTI, Nature

Neuroscience and Trends Journals. The Association of British

Neurologists, The Physiological Society and The British

Neuropathological Society are

also part-sponsoring some

symposia this year . The BNA is

extremely grateful for their

contributions. We have a busy

scientific programme at the

meeting and, as usual, there will

be a full exhibition for members

to catch up with what’s new in kit

and books. However, for the first

time, we are also reaching out to

the world of art. An exhibition of

"art and the brain" will be on

show throughout the meeting,

with collections provided by the

MRC and The Wellcome Trust,

and by private artists. Well worth a visit! Organising the national

meeting is a considerable administrative task and I would like to thank

Yvonne Allen, Vicky Gill and Lucy Williams in the BNA Office for their

tremendous efforts in putting everything together.

DEBBIE DEWAR

● The BNA is also sponsoring and contributing to a number of other

events over the rest of the year. Some of you may have already

attended one of the "Controversial Issues in Neuroscience" discussions

at the Dana Centre, London. These sessions are specifically designed

to stimulate debate amongst both scientists and the public, and the

events last year certainly did that. This year, the series continues with

topics such as "should we prolong life in premature babies", and

"should we use cognitive enhancing drugs?" We are always on the look

out for new topics in this series, so if there’s a burning issue you would

like aired in a public forum with some provocative speakers, please

send in your suggestions (y.allen@bna.org.uk).

● Autumn promises to be a busy time for the BNA. Due to the success

of the first BNA-sponsored Postgraduate and Early Career Symposium

last September, the committee has decided to make this an annual

event. Stephan Przyborski and Chris Thompson have kindly offered to

host the second symposium in Durham this coming September. In

addition to our own events, members are participating in meetings

organised by other societies. In early September, we are contributing

two symposia at the 7th International Congress of the Polish

Neuroscience Society, to be held in Krakow. Mike Stewart has

organised a symposium entitled "Mechanisms of hippocampal

plasticity" and Stefan Przyborski one entitled "Neural differentiation of

non-embryonic stem cells". In October, we are linking up with the Pain

Society for a joint One Day Symposium on Long term potentiation as

a mechanism for pain.

● Finally, to round off the year, our ever-popular Christmas Symposium

will take place in December. Last December’s meeting was a sell-out,

understandably so with such an impressive scientific theme and

programme of speakers. The BNA annual awards for Public Service

and Outstanding Contribution to British Neuroscience were made to

the European Dana Alliance for the Brain and Geoffrey Raisman

respectively. Suggestions and nominations for this year’s theme and

awards can be sent to the BNA Office, as soon as possible please

(y.allen@bna.org.uk).

Ambiguous images generating at least two different percepts; 3-D

structure has been lost in the 2-D projection. See scientific review by

Tamara Curnow, pages 12/13.

Dates for your Diary

● 3rd – 6th April, 2005:

18th National Meeting, Brighton, Sussex, England

● 22nd June, 2005: Controversial Issues in Neuroscience:

‘Premature babies: life at a price?’ A café-bar discussion at

The Dana Centre, London

BNA Symposia at the VIIth International Meeting of the Polish

Neuroscience Society, 7th – 10th September, Krakow, Poland

● 14th – 15th September, 2005:

Post-graduate and early career neuroscientist symposium, at

the University of Durham

● 28th September, 2005:

Controversial Issues in Neuroscience: ‘Cognitive enhancing

drugs – to have or not to have?’ A café-bar discussion at

The Dana Centre, London

● One Day Symposium:

‘Long term potentiation as a mechanism for pain’,

19th October, 2005, at The Open University, Milton Keynes

● 14th December, 2005:

The Christmas Symposium, at The Royal Society, London

The British Neuroscience Association Newsletter is published regularly and distributed to over 2,000 members of the BNA.

The views expressed in the newsletter are the authors’ own and are not necessarily the opinion of the BNA committee.

DEADLINE FOR SUBMISSION OF ITEMS FOR THE NEXT NEWSLETTER: Ist JUNE 2005

The BNA Newsletter is produced by Yvonne Allen in the BNA Conference Office.

Please send any items for inclusion in the next newsletter to:

Newsletter Editor, BNA Conference Office, The Sherrington Buildings, Ashton Street, Liverpool L69 3GE

Tel: 0151 794 5449 / 4943 ✦ Fax: 0151 794 5516 / 5517 ✦ email: newsletter@bna.org.uk

The British Neuroscience Association is registered as a charity (1103852) and as a charitable company (4307833)

ISSN 1475-8679

3


INTERVIEW

Professor Anders Bjorklund visited

Liverpool last November to deliver

the annual Sherrington Lecture that

he entitled: ‘Towards a stem cell

therapy for Parkinson’s disease’. The

BNA took this rare opportunity to

interview face-to-face a major

protagonist about his pioneering

work in the field of foetal tissue and

stem cell transplantation and, in

particular, about the social debate

surrounding this work. As a former

FENS president, he was also asked

to comment on the progress of this

true federation of neuroscience

societies. Here are some of his

thoughts.

What is it about Sweden and Swedish policy

that has allowed you to pioneer work in the field

of neural transplantation?

In the 1980s, we had quite a lively debate around

the ethics of using foetuses because it reactivated

a discussion around abortion and the ethics

surrounding it. Suddenly, we now had a use for the

material, but some who took part in the debate thought that it might

stimulate or increase the number of abortions as it might provide an

incentive for women to undergo abortions. This debate ended up in

the modification of both transplantation law in Sweden and also the

law regulating the use of embryos and foetuses for research

purposes.

We have had a lively debate about the use of human embryonic stem

cells in Sweden now for about four or five years. This resulted in a

new law last year, and we are now moving into the second step of

allowing therapeutic cloning or nuclear transplantation. When that is

implemented, I think the legal situation will be quite similar to that in

the UK.

I don’t think it’s desirable for scientists to do research in a totally free

environment. There has to be a good system for surveillance, and for

the public to feel safe, and that the research is justified and

sufficiently important. If we had no regulations or legislation, it would

be easy to claim that scientists have a free rein to do whatever they

want, and this could easily be discredited. It must be well controlled.

What do you think about the very polarised stem cell debate in

the USA?

It is interesting that it is so polarised in the States and not in the UK

or Sweden. Germany has had a similar problem, in fact, and has

ended up in a discussion where each side is widely separated on the

issue. In the States, I think one main reason is that abortion has

remained a very sensitive issue, and has never been fully accepted by

society. In Sweden and the UK, abortion is generally accepted by the

majority of people.

Time is also an important element for individuals to come to gradually

accept elements of life that would seem upsetting to previous

generations. There are many things in our present society I think that,

three generations ago, would have caused great concern. These can

be lifestyle issues, attitudes or habits. Time has played an important

role, and acceptance comes from getting used to argument, and also

understanding the background and history. There is also the issue of

not being afraid of new things. Things that come without proper time

for reflection may generate more fear and uncertainty than the

familiar.

The UK Press has, in general, hyped stem cell research as the

next great cure for the incurable. Do you think the possibilities

live up to the hype?

It is an unfortunate side effect of the attention to stem cell research

that it has been oversold. The time perspective is totally unrealistic. I

4

‘Time has played an important

role….. Things that come without

proper time for reflection may

generate more fear and

uncertainty than the familiar...’

think what remains important is

that stem cell research has a very

interesting potential, and opens

up new fields of research where

the basis of disease, and

biological phenomena, can be

studied in a controlled system, in

a very different way than has been

possible before.

Regenerative medicine is

something that, maybe in 20 or

more years time, will benefit many

greatly. Whether or not this means

that stem cells themselves will be

used, or the knowledge generated

from studying the various

biological mechanisms, I think is

an open issue. It’s a pity that the

use of stem cells themselves has

been overemphasized when it is

the whole research field that is

important.

Do you not feel that the public

need to hear about the

prospective clinical treatments

so that they can deal with the

ethical issues of the research?

I think it’s an oversimplification of

the discussion. There is truth in

the fact that these cells are opening up very important research

avenues, but the scientific community will not gain from building up

expectations too high, because time is a crucial factor. We need

time to develop this knowledge in the right way. Any attempt to

jump on therapies quickly is bound to be destructive. One possible

consequence of overselling stem cell research is that biotech

companies could get into situations where they are pressed for

clinical application and products too early. Premature application

could be very negative for the field. Patients could be harmed, or

early trials might give negative outcomes.

Do you think it would, therefore, be useful to try to

communicate the concept of the ‘scientific process’ to the

public? For instance, simply pursuing knowledge to increase

the ‘potential’ of a field (like stem cell research) is as justified

as directly pursuing a specific clinical treatment?

There could be a ‘job share’ here. Science has to be simplified for

the public, but there needs to be a balance in the public debate.

Scientists must go out to reach people who are more directly

involved and concerned, such as clinicians, legislators, patient

organisations and the families of patients. They, in turn, should be

able to get access to the research. Patient organisations in

particular, can be very interested in the work being done and want

more detailed information. They have been quite willing to enter

into in-depth discussions. This makes it easier to get the whole

message across.

Finally, a couple of questions about FENS. Are you pleased

with the way FENS has developed over the years?

Yes. The Forum meeting is now well established and the first four

meetings have all been quite successful. The format, size and

scope have lived up to our expectations.

What would be your ambitions for FENS in the future?

I think FENS should take further steps to become a strong lobby

organisation for European neuroscience. I see the European Brain

Council as a good initiative in this direction, and I think FENS

should take an active leadership role within this newly established

lobby organisation.

How could the BNA help to achieve these goals for FENS?

The national organisations, including BNA, are of course the

"owners" of FENS and should remain vital partners in implementing

FENS´ goals. Close collaborations on all levels would be optimal.


OPINION

THE INTERFACE

BETWEEN ACADEMIA

AND INDUSTRY:

AN "ENABLER’S"

PERSPECTIVE

In 1990, Ian Varndell founded AFFINITI

Research Products Ltd., the first reagent

supplier with a focus on neuroscience

research. He is now Vice President of

European Operations for BIOMOL

International L.P., a UK/US manufacturer

of biochemicals and immunochemicals for

life science research. Ian is also a past

Honorary Treasurer of the BNA.

Reagents don’t grow on trees (or,

if they do, they have to be

extracted and purified) – you need

them, we make them, market

them and then we sell them.

That’s how we stay in business.

Two decades! How depressing. It’s

almost 20 years since I left my post

as Lecturer in Histochemistry at the

RPMS (now part of Imperial

College, London) to join a small life

science business based near

Cambridge. Some of the then

unborn are now planning their

postgraduate journeys as early

career scientists, many of my peers have been promoted to senior

levels within their chosen profession, and my mentors are

contemplating retirement or are already engaged in creating the perfect

lawn or a jet black rose. This is a brief personal reflection on how

academic and industrial scientists can make excellent bedfellows.

When I announced I was leaving an academic job to join a company I

was accused by some of "selling out". I’m still not sure what that

means. If it’s that working in an SME (a small or medium-sized

enterprise) is all about wealth, fast cars, long lunches and precious little

science, then I’m still waiting! My company, BIOMOL International, has

R&D and manufacturing operations in both the USA and the UK. In the

UK, we have 14 staff, six of whom hold PhDs. We are a "scientist-rich"

micro-company. There is an important distinction to be made here

between scientists working in pharmaceutical and target-focused

biotech businesses, and those of us who work in the research products

business. The former organisations are there to conduct research with

a drug target goal, whereas my task is to provide some of the products

required by researchers, rather than carrying out research directly. I

think of my job – in fact I consider that the main purpose of the

company – is as an enabler. We make reagents that enable researchers

to carry out their work. This requires my team to be aware of research

trends and have the competence and capability to identify targets, to

make or source, test and support, in a technical sense, all 3000 of the

products in our offering. We are called upon to advise prospective

customers about what they could use in their experiments; we often

become unpaid research planners and sounding boards. One of my

favourite questions was asked by a prospective customer about 15

years ago, "Will your antibody to CGRP work on rabbit uterus?" I didn’t

know, and the datasheet reported results from "mammalian CNS" and

various nerves in the gut and skin. "I don’t know", I answered, then

added - to my mind reasonably – "but if rabbit CGRP is structurally

similar to rodent CGRP, and CGRP-containing nerves exist in the rabbit

uterus, then I am sure that it will". "So you don’t know then", the caller

retorted, and rang off.

Enablers can’t know everything about their reagents. Arguably there

would be no research if we already had all the answers. We do try to

resolve all issues in a single conversation, but failing that we are happy

to enter a dialogue with an agreed goal and a defined strategy to

achieving that goal. We try to achieve the goal with efficiency,

professionalism and good grace, although the frustrations typical

amongst some early career scientists, perhaps brought about by

inexperience, or panic that their PhDs or MRes’s are

in jeopardy, or tiredness and, occasionally, sheer

unadulterated arrogance, can lead to heated

discussions. Is the customer always right? No,

actually they are not, but with positive actions and

lashings of diplomacy (that which a PhD really

teaches you), the enquirer can be left feeling satisfied,

even victorious.

A few years ago, an irate caller accused one of our products of "not

working" in an immunostaining experiment. I asked him to complete a

written questionnaire so I could try to resolve his problem, but he

refused out of hand. He wanted an immediate replacement or refund. I

managed to get him to tell me in sketchy detail the protocol he had

followed. At about point 4 of the protocol, I realised he had made a

mistake that would have led to zero detection of reaction product.

Before I could say anything he, too, must have realised the error and

simply hung up. Another satisfied customer? Maybe. But why the

antagonism in the first place? I don’t suppose he usually

communicated with his colleagues in the manner he spoke to me. Is it

perhaps because scientists in reagent companies are generally

anonymous to end-users as they publish and present less than their

associates in academic, biotech or pharmaceutical laboratories? Are

we perceived by some as mindless peddlers of biochemicals, fleecing

academic budgets to line our own nests, rather than developers of

products that can contribute positively to the advancement of scientific

achievement?

I’d like to think that I am dramatically overstating the view shared by

some of my colleagues – I wouldn’t like to be thought of as paranoid

(I know people stare at me) but sometimes the cap fits. On the other

hand, and much more constructively, many of our valued customers are

often willing to discuss their projects and problems in detail,

occasionally at length, and it is frequently a delight to spar with them

defending our product integrity against charges of inconsistent data

obtainment, using thrusting blows of sarcasm and the odd PowerPoint

image.

Reagents don’t grow on trees (or, if they do, they have to be extracted

and purified) – you need them, we make them, market them and then

we sell them. That’s how we stay in business. Sure, there are some

companies out there who are great at selling, but not so committed to

after-sales service. They do well, and good luck to them, as there are

many reasons why businesses succeed. But I subscribe to the view that

I should know my products and their capabilities better than most of my

customers. I think this attitude has helped my team get invited to

participate in several research collaborations between academia and

the big pharma’. Academic and industrial scientists are in partnership.

We want our products to meet the most exacting standards of our

customers, and see them and their use cited in high impact journals.

We’re here to help.

By Dr Ian Varndell (varndell@affiniti-res.com)

5


BNA NEWS

BNA NEWS

POSTGRADUATE AND UNDERGRADUATE

PRIZE WINNERS 2004:

CONGRATULATIONS!

William Davies (left) congratulated by his

PhD supervisor, Lawrence Wilkinson.

Katherine Carroll

This year’s entrees to the BNA

POSTGRADUATE PRIZE were, as usual,

an exceptionally high standard. The

runners-up were Leigh Felton,

supervised by Hugh Perry in

Southampton, and Tamara Curnow,

supervised by Andrew Parker and

Kristine Krug in Oxford. Leigh

investigated how the chronic expression

of cytokines in the brain, induced either

by viral vectors or chronic degeneration,

led to chronic sickness, or adaptation

and tolerance. Tamara’s thesis compared

the strength of choice probability signal

for near-optimal and sub-optimal rotating

cylinder stimuli in macaque middle

temporal (MT) area. ‘Her work has added

considerably to our understanding about

how decision-related enhancements in

neuronal firing are spread across the pool

of relevant neurons in cortical area MT’,

complemented Andrew Parker. Indeed,

you can read more about her work in the

review article in this issue of the BNA

Bulletin (pages 12/13) Leigh Felton will

be elaborating on his work for our next

issue.

However, the prize this year, after much

deliberation, was justifiably awarded to

William Davies for his outstanding

investigation into the behavioural,

particularly cognitive, effects of X-linked

imprinted genes in mice. ‘We are only

just beginning to realize the potential of

imprinted genes for both normal and

abnormal brain functioning and William

has been to the fore of the debate’,

extolled Lawrence Wilkinson, who

supervised his studies at The Babraham

Institute, Cambridge. ‘[William] showed a

very good understanding of the

impressively wide range of experimental

methods that he had employed on this

ambitious programme of work’,

commented Peter McGuffin, one of his

examiners. Clearly, a worthy winner,

indeed!

Overall, William’s is a timely piece of

work, contributing as it does to both the

increasing evidence implicating genes in

behaviour and emerging ideas that

challenge the current orthodoxy placing

hormonal influences as the sole

determinant of sexual dimorphisms.

Moreover, it points to epigenetic

mechanisms that might contribute to the

marked increased vulnerability of males

to certain mental diseases, in particular

the inflexible ‘stimulus-bound’

behaviours seen in autism.

We are delighted that William, too, has

offered to enlighten us more about his

work by contributing a review article to a

future issue of the BNA Bulletin. Many

congratulations, indeed, to the runnersup

and, in particular, to William Davies

whose thesis shone just a little brighter –

and he gets to spend the £500 prize

money!

The BNA Undergraduate Prize (£250)

this year has been awarded to Katherine

Carroll, an exceptionally gifted medical

student who concentrated on neuroscience

for her intercalated degree in

Physiological Sciences in Oxford last

year. Her undergraduate project was,

coincidently, again supervised by

Andrew Parker and Kristine Krug. Clearly,

their lab is blessed with remarkable

talent, though the quality of supervision

must surely be instrumental in this

success as well.

Katherine used bistable images (a

transparent cylinder with ambiguous

direction of rotation) to probe perceptual

psychophysical mechanisms in the brain.

She found unambiguous stimuli

influenced the perception of ambiguous

stimuli, spreading globally across the

visual field in a manner similar to feature

attention signals spreading across the

visual field representation in the cortex

(the ‘feature similarity gain’ model).

Katherine’s course tutor at Magdalen

College, John Stein, describes her as

‘superlative’ and ‘not at all surprised that

(Katherine) was the top First’. In addition

to her academic prowess, Katherine is

also a talented sportswoman and,

remarkably, also finds time to share her

favourite sport, riding, with

underprivileged and disabled children.

Congratulations, Katherine, for a welldeserved

prize indeed!

6


BNA NEWS

Want to find more

time in the day?

Here’s how i-kode can help you!

The new, free-of-charge i-kode.com service is designed for life

science researchers to help them take control of their mail. When

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kode Partners (vendors of scientific products and services,

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receive mail (and/or e-mail). You can also request removal from

mailing lists or give details of duplicate mailings you receive. All this

is available via a single website.

Then, say you move to another lab, it takes less than a minute to

update your contact details and all of your chosen Partners will

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you to notify each one individually.

Not only does the i-kode.com service save time, it also reduces

waste. As well as reducing duplicate mailings, the service will

reduce the number of items of scientific mail (over 50 million a year

worldwide) that are sent to scientists who are no longer at the

address used. The i-kode.com service also allows colleagues,

such as lab managers or departmental secretaries, to pass on

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removed from mailing lists.

Scientists who have just moved to a new lab find the i-kode.com

service provides a quick and easy way for them to request

information from a number of vendors without having to contact

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is more likely to receive information about products or services that

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Strict procedures are enforced to ensure the confidentiality and

security of personal data stored on the i-kode.com system.

Scientists’ details are only passed to those Partners that the

individual scientist has selected and i-kode.com does not sell or

rent out mailing lists.

Future enhancements to the service will allow groups of scientists

to form online communities, for example to share documents or

diaries online.

Here are some of the things that scientists have said about the i-

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For further information about the i-kode.com service, please

visit www.i-kode.com

Nominations now sought for

the BNA Committee

There will be one vacancy on the BNA

Committee this summer and all members

are eligible to contend for this position. If

you feel you would like to contribute to the

future development of the BNA and really

influence its activities, then why not

consider standing for election? You must

be proposed and seconded by extant BNA

members, and your nomination must reach

the BNA Office by 1st June, 2005. For

further details, contact Yvonne Allen

(y.allen@bna.org.uk, or 0151 794 5449), or

discuss the idea with any of the other

committee members (below).

BNA Committee 2005

Professor Richard Frackowiak (President)

rsjf@fil.ion.ucl.ac.uk

Dr Debbie Dewar (Honorary Secretary):

d.dewar@udcf.gla.ac.uk

Professor Colin Ingram (Treasurer)

c.d.ingram@ncl.ac.uk

Professor Nancy Rothwell (IBRO Rep)

nancy.rothwell@man.ac.uk

Professor Mike Stewart (FENS Rep)

m.g.stewart@open.ac.uk

Dr Duncan Banks (Website Manager)

d.banks@open.ac.uk

Dr Mike O’Neill (Corporate Rep)

oneill_Michael_j@lilly.com

Dr Huseyin Mehmet (co-opted member)

h.mehmet@ic.ac.uk

Dr Elizabeth Warburton (co-opted member)

eaw23@medschl.cam.ac.uk

Dr Richard Ribchester

rrr@ed.ac.uk

Dr Chris Thompson

c.l.Thompson@durham.ac.uk

Dr Stefan Przyborski

stefan.przyborski@durham.ac.uk

Dr Andy King

andrew.king@physiol.ox.ac.uk

Dr Narender Ramnani

n.ramnani@rhul.ac.uk

Secretariat:

Dr Yvonne Allen (Executive Secretary/BNA

Bulletin Editor): y.allen@bna.org.uk

Ms Victoria Gill (BNA Administrator):

vic.gill@bna.org.uk

7


BNA NEWS

BNA NEWS

Geoffrey Raisman accepts his BNA Award from Richard

Frackowiak, with his granddaughter, Clare, by his side.

BNA ‘Award for Public Service’ is presented to Elaine Snell,

on behalf of EDAB.

BNA AWARDS 2004:

Geoffrey Raisman FRS and the

European Dana Alliance for the Brain

On 15th December, 2004, The Royal

Society provided the perfect setting for

the BNA to present its Awards for

‘Outstanding Contribution to British

Neuroscience’ and for ‘Public Service’ to

Geoffrey Raisman FRS and to the

European Dana Alliance for the Brain

respectively.

Taking a brief interlude during the

proceedings of our annual Christmas

Symposium, Professor Richard

Frackowiak, as President of the BNA,

complimented the enormous contribution

Geoffrey Raisman has made, first, to our

understanding of synaptic plasticity in

the nervous system and, then, for his

pioneering work on transplantation into

the CNS. Most latterly, however, Geoffrey

is well known for his recent research on

repairing spinal cord lesions with

implants of olfactory ensheathing cells.

As Director of the newly established

Spinal Repair Unit at UCL, Geoffrey will

oversee some of the most important

clinical trials in this field, bringing hope to

patients who have long considered

themselves incurable.

In accepting the BNA award, Geoffrey

was humbled by the accolade, and, in

particular, praised British scientists in

general who struggle against a sea of

bureaucracy that frustrates and distracts

when, instead, their work should be

encouraged and facilitated by the

Government. He joins a growing list of

eminent previous recipients of this

prestigious BNA award: Pat Wall, Richard

Morris, Tim Bliss and Colin Blakemore.

All BNA members are more than

welcome to make suggestions for future

nominations (contact: y.allen@bna.org.uk).

Richard Frackowiak was then equally

honoured to present the Award for Public

Service to EDAB, an organisation that

works tirelessly to bridge an important

gap between scientists and the public,

encouraging an understanding and

awareness of progress in brain research

that can only enhance for the better our

relationship with the people who, after all,

largely fund our science. As executive

officer for EDAB, Elaine Snell was clearly

delighted to be receiving the Award on

EDAB’s behalf, and spoke highly of the

mutual benefits of the BNA’s

collaboration with EDAB over many

diverse and varied activities, ranging

from Brain Awareness Week, to the

‘Controversial Issues in Neuroscience

series of café-bar discussions at The

Dana Centre, established last year and

set to continue throughout 2005 as well.

Clearly, EDAB was a popular and

deserving choice for 2004. Again, BNA

members can submit ideas or suggestions

for future recipients at any time.

SPECIAL OFFER CONTINUES!

'Neuroscience - Science of the Brain: an introduction for young students'

In late summer, 2003, all schools, colleges and

every BNA member were sent a copy of our

booklet 'Neuroscience - Science of the Brain: an

introduction for young students’. Primarily aimed

at intelligent sixth formers considering

neuroscience as a degree option, you may have

noticed the booklet is also ideal as a general

introductory text for first year undergraduates as

well. For a limited period, the BNA made the

booklet available at only £3.99 including postage

and packaging (reduced from £7.99). The BNA

has decided to extend this popular offer for the

rest of this year to allow our members another

opportunity to order this excellent publication for

students and others. What better way to

welcome your students to their degree course,

or to persuade others into neuroscience!

Please email: info@bna.org.uk or telephone

0151 794 5449 if you require further

information, or wish to place an order.

DON’T MISS OUT ON THIS SPECIAL OFFER!

8


BNA EVENTS

18th National Meeting

The Brighton Centre

Brighton

3rd to 6th April, 2005

REGISTRATION CONTINUES ON-LINE AND ON-SITE!

Our 18th National Meeting will shortly be held at The Brighton Centre, and will feature an eclectic range of plenary

lectures, twenty symposia and more than 50 themed poster sessions as part of an exciting scientific programme.

All abstracts will be published by the BNA (ISSN 1345-8301). In addition, there will be an exhibition representing

nearly 30 companies and a fascinating array of peripheral events, including ‘teaching of neuroscience’ and ‘public

awareness of science’ discussion groups, and a presentation on the latest OST Foresight initiative on ‘Brain

science, addiction and drugs’. There will also be a number of social gatherings for delegates to enjoy, in particular

the legendary BNA party night! So do come and join us for this wonderful neuroscience extravaganza by the seaside

in this most Bohemian of English towns! Checkout the website for the latest updates on all the events, scientific

and social, and for travel and accommodation information!

www.bna.org.uk/brighton2005/

PLENARY SPEAKERS:

Marie Filbin (New York) ◗ Tamas Freund (Hungary)

Pierre Magistretti (Lausanne) ◗ James McCulloch

(Edinburgh) ◗ Hugh Perry (Southampton) ◗ Trevor

Robbins (Cambridge) ◗ Peter Seeburg (Heidelberg)

SYMPOSIA:

● Plasticity of GABA-A receptor gene expression:

molecular mechanisms

● Does synaptic plasticity provide the substrate for

learning and memory?

● Strategies for repair after spinal cord injury

● Progress in stem cell biology

● The importance of human neuropathology for

neuroscience research

● Regulation of serotonergic neurotransmission and its

relevance to mood

● Information coding in the auditory cortex

● Sensory integration for cognition and action

● Models of neurodegeneration

● Neuroinflammation: protagonists and antagonists

● Stem Cell Plasticity: can stem cells cross lineage

boundaries?

● Curing Parkinson's: progress on molecular and cellular

biology of the disease and on therapies to

neuroprotect and repair the brain

● Advances in Magnetic Resonance methodology

● Role of microglia in brain injury

● Promoting recovery after stroke

● Addictive behaviour

● The enteric nervous system: function, development

and ageing of a complex peripheral neural network

● Animal modelling of psychiatric disease

● Gene silencing in the brain: functional genetics and

therapeutics

● From spikes to sensation

For further details:

BNA2005@bna.org.uk, tel: 0151 794 5449.

Website: www.bna.org.uk/brighton2005/

9


BNA EVENTS

CONTROVERSIAL ISSUES IN

NEUROSCIENCE

‘PREMATURE BABIES: LIFE BUT AT WHAT PRICE?

A cafe-bar discussion to discuss the long term consequences and ethical issues of prolonging life in premature babies.

Organized in partnership with the European Dana Alliance for the Brain

6.30pm, Wednesday, 22nd June, 2005, at The Dana Centre, 165 Queens Gate, London SW7

(at the rear of the Science Museum)

Speakers include Huseyin Mehmet (Imperial College), Kate Costeloe (Homerton Hospital and EPIcure Study), and Richard

Parnell (Head of Research and Public Policy at Scope). The discussion will be chaired by Anjana Ahuja (The Times)

Admission FREE for BNA members and their guests.

Contact:

events@bna.org.uk; tel: 0151 794 4943/5449

POSTGRADUATE AND

EARLY CAREER

SYMPOSIUM

14th – 15th September, 2005,

at the University of Durham

This year’s symposium will host a themed workshop on

‘Communicating Science’, and will feature expert talks on

how to communicate research to the public and the media,

or to other scientists at conferences, or to other students

in a teaching environment. There will also be an

opportunity for young investigators to present their work

as oral communications and be offered personal advice on

presentation skills.

Registration fee: £50 for BNA members: £75 for nonmembers.

Fee will include all refreshments, lunches and

evening reception, and all documentation. Accommodation

will be available in Halls of Residence, £38 per night,

en-suite and inclusive of full English breakfast.

For further information:

events@bna.org.uk.

Tel: 0151 794 4943/5449.

Registration opens: 1st May.

Abstract deadline: 31st July, 2005

ONE DAY

SYMPOSIUM

LONG TERM

POTENTIATION AS A

MECHANISM FOR PAIN

An opportunity for basic neuroscientists and clinicians to

liaise and discuss the latest advances in pain research

Wednesday, 19th October, 2005, at

The Open University, Milton Keynes

To be held in collaboration with The Pain Society

Chaired by:

Paul Watson (Leicester) and Maria Fitzgerald (London)

Speakers include:

Tony Dickenson (London), Irene Tracey (Oxford),

Walter Magerl (Mainz), Jürgen Sandhüler (Vienna), Bill

McCrae (Dundee), Geert Crombez (Gent)

Admission is FREE for members of the BNA

(non-members £60 / student non-members, £25)

For further information and ticket reservations:

events@bna.org.uk ● Tel: 0151 794 4943/5449

10


BNA EVENTS

VIIth National Congress of the

Polish Neuroscience Society

7th – 10th September, 2005, Krakow, Poland

The BNA is collaborating with the Polish Neuroscience Society this year by contributing

two special symposia at their National Meeting.

A small number of bursaries will available for BNA student members

wishing to present at this congress.

MECHANISMS OF HIPPOCAMPAL

PLASTICITY

Friday, 9th September, 2005

CHAIRED BY: MIKE STEWART (OPEN UNIVERSITY, UK) AND MALGORZATA KOSSUT (NENCKI INSTITUTE)

SPEAKERS:

Dmitri Rusakov (Institute of Neurology, London)

Activity-dependent control of rapid presynaptic Ca2+ signalling at individual central synapses

Ralf Schoepfer (University College, London)

Low expression levels of NR1 N598R NMDA receptors alter functional and structural properties

of the dentate gyrus, and impair spatial learning

Zafar Bashir (University of Bristol)

Glutamate receptors and synaptic plasticity

Mike Stewart (Open University, Milton Keynes)

Structural basis of hippocampal plasticity

‘NEURAL DIFFERENTIATION OF

NON-EMBRYONIC STEM CELLS’

Saturday, 10th September 2005

CHAIRED BY:

Stefan Przyborski (Durham)

SPEAKERS:

Roger Barker (Cambridge)

Using stem cells to repair the Parkinsonian brain: Will this ever work?

Angelo Vescovi (Italy)

Neural stem cells in brain pathology and therapy

Siddhartha Chandran (Cambridge)

Adult solutions for adult problems

Stefan Przyborski (Durham)

The success and failure of neural development by non-embryonic stem cells.

For further information: events@bna.org.uk; tel: 0151 794 4943/5449

For registration and abstract submission: website: www.targi.krakow.pl

11


SCIENTIFIC REVIEW

Seeing is believing:

Tough decisions in a visual world

Tamara Curnow recently completed her DPhil in Oxford under the auspices

of Andrew Parker and Kristine Krug. As runner-up for the BNA Postgraduate

prize this year, Tamara was invited to contribute a review article on her work

to the BNA Bulletin, such was the impression she left with the panel of judges.

She recounts here the role of the middle temporal area in the decision-making

processes that make sense of our visual world.

‘….our decisions are not only based on external

stimuli; we often combine visual information with our

own past knowledge and experience. For instance, we

know that pink elephants are rare, except in cartoons’.

When we open our eyes, we are inundated with visual information

with which we navigate through our lives and, each day, we make

thousands of decisions based on this visual input. However, our

decisions are not only based on external stimuli; we often combine

visual information with our own past knowledge and experience.

For instance, we know that pink elephants are rare, except in

cartoons. Thus, somewhere in the decision-making pathways,

stimulus-based information must be combined with more cognitive

inputs.

The contribution of individual neurons to decision-making can be

investigated by measuring differences in neuronal activity when

different choices are made (choice-related response). One difficulty

is that an individual’s choice in psychophysical experiments is often

inextricably linked with the stimulus, and changes in the stimulus

also tend to alter neuronal responses. Thus, any choice-related

activity will often be obscured by the neuronal responses to

stimulus changes.

One way to separate neuronal responses to the stimulus from

responses related to the choice is to study tasks where the

observer makes different decisions on subsequent viewings of the

same stimulus (see front cover, for example). Subjects perceive

different configurations of ambiguous stimuli on different viewings.

This means that there are neurons responding differently on

subsequent presentations of the same stimulus, giving rise to the

alternative choices.

How might the correlation between the observer’s choice and the

neuronal response be investigated? Certainly, neuronal activity

must be measured whilst the subject makes a decision. This is only

possible in awake animals trained to perform a task with (at least)

two different possible perceptual responses. In addition, an

electrode must be inserted into the relevant brain area to record the

neuronal activity. The different responses of the animal must be

compared with the different responses of the neuron over several trials.

One cortical area where choice-related responses have been

studied is the middle temporal area (MT) of the macaque visual

cortex [1]. Responses of MT neurons are modulated by changes in

stimulus parameters such as the direction of moving stimuli and the

distance of stimuli from the observer [2, 3]. In addition, microstimulation

of MT has been shown to bias animals’ judgments

about the motion or depth of visual objects [4, 5]. Finally, MT

responses are correlated with the choice made by the animal in a

number of two-alternative forced-choice tasks, even on trials where

the stimulus is ambiguous (and so no stimulus-related signal is

present) [6-8]. Thus, MT neurons contribute to decisions about

motion and depth stimuli.

The correlation between neuronal and psychophysical response

varies between different tasks. Motion [6] and depth [8]

discrimination tasks have been used to measure choice-related

responses in MT. The correlation between choice and neuronal

response for both these tasks was weak but nonetheless

(Figure 2)

significant. Another stimulus used to

investigate MT choice-related activity

is the rotating random dot cylinder

defined by structure-from-motion [7]

(Figure 2). This stimulus is a patch of

dots where each dot moves as

though it were painted on the side of

a 3D rotating cylinder viewed from

the side. The depth between the

faces of the cylinder can be varied

and this allows the direction of

rotation to be changed. When the

depth cue is zero, the cylinder’s

direction of rotation is ambiguous.

Unlike the motion and depth stimuli,

no dots in the cylinder carry

misleading information. Even when

ambiguous, the cylinder is perceived

rotating in one direction and is stable

for many seconds. Possibly because

of these differences, a much higher

(Figure 1)

correlation has been reported

between MT neuronal responses and

the animal’s choices for the cylinder than for other studies [6-8].

So MT contributes to decisions about certain visual stimuli but

there are still many unanswered questions. For example, what is

the extent of the choice-related activity in MT? Which MT neurons

contribute to the decision? Is the MT choice-related activity purely

stimulus-driven? Or are the more cognitive inputs to the decision (the

animal’s experience, strategy, attention etc.) reflected in the

response? These are some of the questions that my work addressed.

In neurophysiology experiments, it is common for the majority of

visual stimulus parameters to be adjusted so that the recorded

neuron responds optimally. Indeed, in previous experiments

investigating choice-related activity in MT [6-8], most stimulus

parameters were optimised except the one varied systematically as

part of the protocol (e.g. the strength of the motion or depth cue).

Thus, choice-related activity was only recorded in neurons with the

largest response to the presented stimulus. We do not know what

contribution sub-optimally stimulated neurons make to decisions.

There are two reasons for considering neuronal responses to suboptimal

stimuli. Firstly, in the everyday world we encounter many

visual stimuli and so individual neurons are rarely optimised outside

the laboratory. Secondly, neurons often respond significantly to

stimuli that are not optimal and it is unlikely that these responses

(and the energy consumed in generating them) are wasted.

I investigated the role of sub-optimally stimulated neurons in

decision-making. I used the random dot cylinder because it was

the stimulus for which the highest choice-related activity was

recorded for optimised stimuli and so had the most scope for

12


SCIENTIFIC REVIEW

investigating changes. I recorded extra-cellularly from single MT

neurons in two awake, behaving macaques. The animals

performed a two-alternative forced-choice task, discriminating the

rotational direction of a random dot cylinder (over the neuron’s

receptive field) by making an eye-movement to one of two choice

targets. The cylinder axis was either optimally oriented for the

recorded neuron or at a sub-optimal orientation, generating a

significantly lower firing rate. In addition, the depth between the

surfaces of the cylinder was varied from trial to trial to check that

the monkey was genuinely performing the task, (reporting the

stimulus direction of rotation) and not simply picking targets at

random. I interleaved both ambiguous and unambiguous trials at

both optimal and sub-optimal orientations.

For each neuron, I calculated the choice-related response to

ambiguous stimuli that were optimally and sub-optimally oriented.

My analysis showed hardly any reduction in the mean MT choicerelated

activity for sub-optimally oriented stimuli.

This result has implications in modelling MT’s role in decisionmaking.

It means that neurons responding sub-optimally potentially

contribute as much to decision-making as those responding

optimally. It also tells us about the

localisation of these neurons

because MT is highly structured;

nearby neurons show very similar

tuning properties changing smoothly

across the cortical surface. My

results suggest that the potential

pool of MT neurons contributing to the decision is not localised just

to the column of neurons responding optimally to the stimulus but

extends to neurons further away in MT. Models, therefore, cannot

be constrained by the geometric proximity of the contributing

neurons.

Modellers of decision-related activity are concerned about the

source of signals contributing to the decision. The stimulus-based

information originates in the retina and passes to MT via the

thalamus and the primary visual cortex. However, for ambiguous

stimuli there is no stimulus information to distinguish the two

choices. Is there a separate, more cognitive signal determining the

choice? Or is the choice determined by randomness in the firing

rates of stimulus-driven neurons, pushing the decision in favour of

one of the options? Shadlen et al. (1996) [9] modelled the data from

the motion discrimination task [6] and found that trial-by-trial

fluctuations in neuronal response could explain the MT choicerelated

activity. I applied the Shadlen model to my data and found

that it did not account for the high choice-related response in the

cylinder task. This suggests that area MT might play a quite

different role in the two tasks. A non-stimulus based ‘choice signal’

[7] input to MT in the cylinder task might account for the different

‘….as we understand more about the

combination of visual and cognitive signals

we will start to build a better model of the

physiological basis of decision-making’.

choice-related responses for the cylinder and the motion stimuli.

Such a signal might also explain the wider reaching choice-related

response found across columns of different orientation selectivity.

Another aspect of decision-making is the incorporation of past

knowledge or experience. There are many potential strategies

available when embarking on psychophysical tasks. For example,

if an observer is rewarded less for correctly choosing one target

than for correctly choosing the second he might be more cautious

about selecting the first. Some strategies are not founded on any

aspect of the experimental design. For example, I found that if the

monkey was rewarded on an unambiguous trial he tended to adopt

one of two strategies on the subsequent ambiguous trial: either

win-stay where he chose the same target as was previously

rewarded or win-switch where he chose the opposite target. The

stimuli were pseudo-randomly ordered and so he made no gain by

adopting either strategy. The monkey’s strategy was fairly

consistent across a recording session, although on any particular

day either strategy might have been adopted.

Any psychophysical bias must have a neuronal correlate at some

point in the decision-making pathway. I separated the neurons

according to the psychophysical

strategy adopted by the monkey

(measured simultaneously). Over the

first 500 ms of the trial, I found a

significant difference in MT response

depending on the direction of rotation

in the preceding trial when the

accompanying psychophysics was win-stay but that the difference

disappeared when the strategy was win-switch.

Thus, there is evidence of the monkey’s strategy in the MT

response despite the early position of MT in the visual stream. The

implications for models of decision-making are profound. These

results indicate that most of the information required for forming

decisions is accumulated at or before MT. Evidence from the

parietal cortex [10] suggests that the MT response is integrated

over time and, when sufficient evidence is attained in favour of one

choice, the motor response is initiated to achieve the reward.

In summary, I examined the contribution of MT neurons to

decisions made in psychophysical tasks. The MT response

modulates with the stimulus the choice and the strategy adopted

by the animal. Understanding these modulations in response, in

particular their magnitude and their time course, is critical to

understanding how decisions are made about simple visual stimuli.

In reality, our lives are more complex than external stimuli directly

initiating motor responses but as we understand more about the

combination of visual and cognitive signals we will start to build a

better model of the physiological basis of decision-making.

FIGURE LEGENDS Figure 1. An ambiguous picture: A "Shade of Napoleon" is hidden in the trees overlooking his tomb. Figure 2. The random dot

cylinder is a patch of random dots (a) each with a sinusoidal velocity profile (b) such that the percept is a rotating cylinder (c).

1. Zeki, S.M., Convergent input from the striate cortex (area 17) to the

cortex of the superior temporal sulcus in the rhesus monkey. Brain

Research, 1971. 28: p. 338-340.

2. Dubner, R. and S.M. Zeki, Response properties and receptive fields

of cells in an anatomically-defined region of the superior temporal

sulcus in the monkey. Brain Research, 1971. 35: p. 528-532.

3. Maunsell, J.H.R. and D.C.V. Essen, Functional properties of neurons

in middle temporal visual area of the macaque monkey. II Binocular

interactions and sensitivity to binocular disparity. Journal of

Neurophysiology, 1983. 49: p. 1148-1167.

4. Salzman, C.D., et al., Micro-stimulation in visual area MT: effects on

direction discrimination performance. Journal of Neuroscience, 1992.

12: p. 2331.

5. DeAngelis, G.C., B.G. Cumming, and W.T. Newsome, Cortical area

MT and the perception of stereoscopic depth. Nature, 1998. 394: p.

677-680.

by Tamara Curnow (tamara.curnow@physiol.ox.ac.uk)

6. Britten, K.H., et al., A relationship between behavioral choice and the

visual responses of neurons in macaque MT. Visual Neuroscience,

1996. 13: p. 87-100.

7. Dodd, J.V., et al., Perceptually bistable three-dimensional figures

evoke high choice probabilities in cortical area. Journal of

Neuroscience, 2001. 21: p. 4809-4821.

8. DeAngelis, G.C. and T. Uka, Coding of horizontal disparity and

velocity by MT neurons in the alert macaque. Journal of

Neurophysiology, 2003. 89: p. 1094-1111.

9. Shadlen, M.N., et al., A computational analysis of the relationship

between neuronal and behavioral responses to visual motion. Journal

of Neuroscience, 1996. 16: p. 1486-1510.

10. Shadlen, M.N. and W.T. Newsome, Neural basis of a perceptual

decision in the parietal cortex (area LIP) of the rhesus monkey.

Journal of Neurophysiology, 2001. 86: p. 1916-1936.

13


SCIENTIFIC REVIEW

THE CHICK BRAIN - WHY BOTHER?

Mariangella Nikolakopoulou was a PhD student working with

Professor Mike Stewart in the Department of Biological Sciences at

The Open University, Milton Keynes. Now a post-doctoral research

worker in the University of California (Irvine), she describes how and

why many regions of the chick brain respond variously to passive

avoidance learning. How does this compare to mammals?

Fig. 1: Two BrdU labelled

cells stained with Cy5

(arrowed). One of them is

located on a glial fiber (GFAP

stained with FITC, arrowed).

A mushroom spine contacts a dendrite

creating an asymmetric shaft synapse.

Fig. 1 Fig. 2

Fig.2: A double labelled cell

for BrdU and NeuN (nuclear

neuronal marker) - arrowed.

Many studies support the idea that several areas of the chick

brain are homologous to areas of the mammalian brain. The

hippocampus is of great importance to the mammalian brain

because it plays a key role in the acquisition and retention of

declarative, contextual and spatial memory. The chick

hippocampus, although a much simpler structure because of

lack of layers, has been proven to have a number of similar

functions. The latter can be divided into dorsal and ventral parts

based on immunocytochemical (Erichsen et al., 1991) and

tracing techniques (Szekely, 1999) or electrophysiological data

(Siegel et al., 2002). The ventral hippocampus is equivalent to

Ammon’s horn while the dorsal hippocampus is corresponding

to the dentate gyrus (Szekely and Krebs, 1996) and the area

parahippocampalis (APH) is comparable to the subiculum

(Casini et al., 1986).

Recent studies (Dermon et al., 2002) have shown that one-trial

passive avoidance learning (PAL) enhances cell proliferation in

IMM (intermediate medial mesopallium), which is an area

strongly associated with memory, StM (striatum mediale) and

TuO (tuberculum olfactorium) 24 hours and nine days post-BrdU

injection. The passive avoidance learning paradigm is based on

the inclination of young chicks to peck at small objects which

will include round beads. A chick is presented with a small

chrome bead dipped either in water or in a very bitter tasting

substance called methylanthranilate (MeA). Chicks that

experience a water-coated bead peck thereafter whereas, if they

have tasted MeA, they avoid the bead, instead showing signs of

stressful behavior.

Neurogenesis has been identified in the chick hippocampus

after food storing processes (Clayton and Krebs, 1994). Barnea

and Nottebohm (1994) have stated that the rate of neurogenesis

in the different regions of the avian hippocampus is influenced

by seasonal changes, whilst Patel et al. (1997) refers to an

increase in neurogenesis after spatial learning. However, no

studies after passive avoidance training have been reported so

far to indicate the effects of the above-mentioned training on cell

proliferation in the hippocampus.

The purpose of these studies was to examine the effects of

passive avoidance learning (PAL) in the chick hippocampus and

then expand to other areas of the limbic system, the

arcopallium, the nucleus taeniae of amygdala and, finally, the

olfactory bulb. Previous studies from Sandi et al. (1992) have

revealed that hippocampal lesions cause amnesia for passive

avoidance training and recent studies (Unal et al., 2002) have

shown the effects of PAL on synaptic density in this region.

The arcopallium, which is a large and heterogeneous structure,

can be divided into at least two major parts. The AI (intermediate

arcopallium) is considered to be responsible for fear responses

in pigeons and chickens (Philips and Youngren, 1971), while the

dorsal (which is not a limbic area) is involved in somatic

sensorimotory system (Zeier and Karten, 1971). Lesions of the

arcopallial formation cause impairments for the acquisition and

retention of PAL (Benowitz, 1972; Lowndes et al., 1994).

Nucleus taeniae of amygdala is a nucleus within the posterior

and medial arcopallium and is believed to be homologous to the

medial nucleus of amygdala (Me) in mammals. Recent studies

have proven that it plays a role in male sexual behavior and is

part of the limbic system (Absil et al., 2002).

The olfactory bulb shows connectivity with the arcopallium and

previous studies have confirmed that it shows neuronal activity

after odor experiments (McKeegan, 2002). Richard and Davies

(2000) demonstrated that training chicks with an odorless

substance did not help the animals to remember PAL as well as

when methylanthranilate (which has a very intense smell) was used.

In our studies, cell proliferation was examined at 24hours and

nine days post-BrdU injection in the hippocampus (Hp), the

dorsal and ventral intermediate arcopallium (AD and AI

respectively) the nucleus taeniae of amygdala (TnA) and the

olfactory bulb (BO). BrdU is an analogue of thymidine and is

incorporated into the DNA during the S-phase of the cell cycle.

Our results indicate a 47% reduction in cell proliferation 24

hours post-BrdU injection in the dorsal hippocampus of the

MeA-trained animals in relation to controls. This finding was

surprising because it appears to contradict the results of the

study in the IMM. Although the explanation is unclear, there are

two possible hypotheses that could elucidate this discovery.

One reason might be that cells undergo higher apoptosis in the

MeA-trained animals in comparison with the controls. However,

apoptotic studies 24 hours after BrdU administration did not

reveal any differences in the number of apoptotic cells, but it is

possible that apoptosis occurs over different time scales to

those which we have examined so far. Another explanation may

be that the passive avoidance training is a stressful condition

that affects hippocampus as it would occur in mammals.

Previous studies (Sandi and Rose, 1997) indicate that the levels

of plasma corticosterone are significantly higher in the MeAtrained

group with regard to controls. Stress effects in the chick

hippocampus may be expressed in terms of a reduced

proliferative rate, as is found in rat brain, and especially in the

dorsal hippocampus which is equivalent to the dentate gyrus.

Double labeling studies that we performed with the use of BrdU

and NeuN (nuclear neuronal marker), and visualized under a

confocal microscope, show reduced NeuN positive cells in the

14


SCIENTIFIC REVIEW

dorsal hippocampus in respect to control animals. This finding

leads us to the suggestion that stress in the chick brain reduces

neurogenesis, while it does not affect the number of glial cells

(GFAP studies).

Cell proliferation is increased in the AI of the MeA-trained group

in relation to the AD. Since AI responds to fear, it would also

likely be affected by stress. The amygdala in mammals is

activated by high stress and learning, so it may be that the same

effect happens in the avian brain. The effects of passive

avoidance training are expressed differently in the arcopallium

and the hippocampus. One possibility for this result may be

related to differential responses to stress and fear following the

avoidance training experience. The AD, on the contrary, is not

affected because it does not belong to the limbic system. No

differences are shown in the nucleus taeniae of amygdala

between the different groups.

The BO of the MeA-trained animals shows significantly elevated

cell proliferation with regard to controls (95%) and water-trained

animals (71.4%). It is known that chicks react to smell and, since

MeA has such a strong odor, it appears to have an effect on that

particular area.

Nine days post-BrdU injection, all of the areas show reduced

cell proliferation in comparison with the animals sacrificed 24

hours after BrdU injection. Our assumption is that cells migrate

to other areas of the brain that we haven’t so far tested.

Apoptotic studies 24 hours, five and nine days post-BrdU

injections did not demonstrate any differences in cell death

either between groups, or amongst the distinct times examined.

To examine changes in synapse formation, animals were

sacrificed six hours and 24 hours after training. Our data

suggests that the density of asymmetric synapses onto spines

increases in the dorsal hippocampus of the right hemisphere in

controls in relation to both the dorsal hippocampus of the right

hemisphere of the MeA-trained animals and controls sacrificed

24 hours after training. The density of asymmetric synapses onto

dendrites is significantly higher in the dorsal hippocampus of the

right hemisphere of control animals in comparison with the MeAtrained

group, a result that opposes previous studies (Unal et al.,

2002). It is noteworthy that, six hours after training, there is an

increase in the number of symmetric synapses onto dendrites in

the ventral hippocampus of the left hemisphere of the MeA group

in respect to controls which disappears at 24 hours.

Radioimmunoassay measurements of cortisol in chick forebrain

tissue demonstrated a longer term increase in levels of steroid in

the chick hippocampus compared to arcopallium and striatum

mediale 20 minutes after training, indicating that passive

avoidance learning is a stressful experience which may explain

synaptic density and cell proliferation reduction observed after

such training.

In conclusion, so far these studies have shown that the passive

avoidance training causes neural and synaptic changes to the

avian brain in a diverse mode for each area examined. Future

studies of other brain nuclei may reveal more secrets about the

function and behavior of the "bird brain".

Absil, P., Braquenier, J.B., Balthazart, J. & Ball,

G.F. (2002) Effects of lesions of nucleus taeniae

on appetitive and consummatory aspects of

male sexual behavior in Japanese quail. Brain

Behav Evol, 60, 13-35.

Altman, J. & Das, G.D. (1965) Autoradiographic

and histological evidence of postnatal

hippocampal neurogenesis in rats. J Comp

Neurol, 124, 319-335.

Alvarez-Buylla, A. & Nottebohm, F. (1988)

Migration of young neurons in adult avian brain.

Nature, 335, 353-354.

Barnea, A. & Nottebohm, F. (1994) Seasonal

recruitment of hippocampal neurons in adult

free-ranging black-capped chickadees. Proc

Natl Acad Sci U S A, 91, 11217-11221.

Benowitz, L. (1972) Effects of forebrain

ablations on avoidance learning in chicks.

Physiol Behav, 9, 601-608.

Bingman, V.P., Ioale, P., Casini, G. & Bagnoli, P.

(1990) The avian hippocampus: evidence for a

role in the development of the homing pigeon

navigational map. Behav Neurosci, 104,

906-911.

Casini, G., Bingman, V.P. & Bagnoli, P. (1986)

Connections of the pigeon dorsomedial

forebrain studied with WGA-HRP and 3Hproline.

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Clayton, N.S. & Krebs, J.R. (1994) Hippocampal

growth and attrition in birds affected by

experience. Proc Natl Acad Sci U S A, 91,

7410-7414.

Dermon, C.R., Zikopoulos, B., Panagis, L.,

Harrison, E., Lancashire, C.L., Mileusnic, R. &

Stewart, M.G. (2002) Passive avoidance training

enhances cell proliferation in 1-day-old chicks.

Eur J Neurosci, 16, 1267-1274.

Erichsen, J.T., Bingman, V.P. & Krebs, J.R.

(1991) The distribution of neuropeptides in the

dorsomedial telencephalon of the pigeon

(Columba livia): a basis for regional

subdivisions. J Comp Neurol, 314, 478-492.

Foidart, A., Tlemcani, O., Harada, N., Abe-

Dohmae, S. & Balthazart, J. (1995) Pre- and

post-translational regulation of aromatase by

steroidal and non-steroidal aromatase

inhibitors. Brain Res, 701, 267-278.

Lee, D.W., Miyasato, L.E. & Clayton, N.S. (1998)

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natural environment: neurogenesis and growth

in the avian and mammalian hippocampus.

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Lowndes, M., Davies, D.C. & Johnson, M.H.

(1994) Archistriatal lesions impair the acquisition

of filial preferences during imprinting in the

domestic chick. Eur J Neurosci, 6, 1143-1148.

Martinez-Vargas, M.C., Stumpf, W.E. & Sar, M.

(1976) Anatomical distribution of estrogen target

cells in the avian CNS: a comparison with the

mammalian CNS. J Comp Neurol, 167, 83-103.

McKeegan, D.E. (2002) Spontaneous and odour

evoked activity in single avian olfactory bulb

neurones. Brain Res, 929, 48-58 .

Patel, S.N., Clayton, N.S. & Krebs, J.R. (1997)

Spatial learning induces neurogenesis in the

avian brain. Behav Brain Res, 89, 115-128.

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stimulation and species-typical behaviour:

activities evoked by electrical stimulation of the

brains of chickens (Gallus gallus). Anim Behav,

19, 757-779.

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methyl anthranilate and denatonium benzoate

as aversants for learning in chicks. Physiol

Behav, 70, 521-525.

Sandi, C. & Rose, S.P. (1997) Trainingdependent

biphasic effects of corticosterone in

memory formation for a passive avoidance task

in chicks. Psychopharmacology (Berl), 133,

152-160.

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a passive avoidance task in day-old chicks.

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Herz, R.S. (1989) The hippocampal complex of

food-storing birds. Brain Behav Evol, 34,

308-317.

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hippocampal unit activity: a basis for regional

subdivisions. J Comp Neurol, 445, 256-268.

Szekely, A.D. (1999) The avian hippocampal

formation: subdivisions and connectivity. Behav

Brain Res, 98, 219-225.

Szekely, A.D. & Krebs, J.R. (1996) Efferent

connectivity of the hippocampal formation of

the zebra finch (Taenopygia guttata): an

anterograde pathway tracing study using

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Unal, B., Bradley, P.M., Sahin, B., Canan, S.,

Aslan, H. & Kaplan, S. (2002) Estimation of

numerical density and mean synaptic height in

chick hippocampus 24 and 48 hours after

passive avoidance training. Brain Res Dev Brain

Res, 136, 135-144.

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(1999) Running increases cell proliferation and

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hermaphrodite teleost. Neuroreport, 12,

2477-2481.

15


SCIENCE AND COMMUNICATION

Your amazing brain!

Penny Fidler

Penny Fidler studied for her doctorate in the Cambridge Centre for Brain

Repair before moving to Bristol in 1999 to set up the Your amazing brain

exhibition in At-Bristol. Since then, she has worked on many projects

including setting up a genetics website in 10 different languages, and, most

recently, ‘Curiosity’, an exhibition that includes a tilted room that creates all

sorts of perceptual ambiguities. Exciting stuff! But, first, she describes for us

the varied work and the original aims and objectives of the award-winning At-

Bristol Science Centre

Are you right or left-eyed? Why do you fall in love? Can you

understand facial expressions? How do you learn and what does

your brain feel like? These are all questions that our visitors

investigate at Explore-at-Bristol.

At-Bristol is a millennium science and discovery centre, where

every exhibit is hands-on and interactive, inspiring visitors to

explore science by investigating their ideas and testing their

predications. We opened to the public four years ago and have now

had over two million visitors.

Since opening we’ve been developing innovative ways to present

brain science to the public. Nearly half of the science centre is

dedicated to ‘Your amazing brain’, making it one of the world’s

largest brain exhibitions. We get visitors from science centres

around the world coming to see how we engage people in the

wonders of neuroscience.

We run regular shows and events for our visitors. The really brainy

show promises a ‘mind-boggling family show to twist your brain,

trick your eyes and amaze you with confusing brain capers’.

By developing collaborations with scientists, we ensure we’ve got

cutting edge research in our exhibitions, particularly the ‘Live

Science Zone’. We also run a series of meet the expert sessions

where local neuroscientists are available to chat with visitors and

answer their questions.

As part of these collaborations with scientists, we entice people to

take part in real science experiments. For example, the world’s

largest maths experiment , a study into right and left handedness,

and a survey on perceptions of infertility which informed

government policy.

With NESTA-funding we’ve created brain games, a unique

experience where 11-15 year-olds spend a week with us exploring

all aspects of the brain – a programme that was so successful that

it’s been expanded into science centres across the country and

inspired the creation of hundreds of games related to the brain.

In January, we were delighted to be voted winner of the best

education website in the UK 2004 by Yahoo. The website,

www.youramazingbrain.org, is funded by The Wellcome Trust and

is a place where people around the world can explore brain

science, take part in real-life experiments and test their brains with

our games, illusions and brain-benders.

Public Debate

One of At-Bristol’s main aims is to get people talking and thinking

about science. We want to engage the public in debate and get

people examining evidence, asking questions, looking at issues

from several points of view and forming their own opinions on what

is permissible in society.

There are many issues in neuroscience, such as the use of stem

cells to treat Parkinson’s disease, that need public debate built into

the policy making process.

Since we work so closely with both scientists and the public, yet

are independent of any government or scientific establishment, we

are ideally placed to host public debates and consultations. We are

increasingly seen as a ‘hub’ for these discussions, the results of

which are used by policy makers in Westminster, local government

and research councils.

Neuroscience in Schools

A’ level Psychology has exploded in popularity. There are now more

A’ level students taking psychology, than biology and chemistry

combined. At-Bristol runs psychology workshops and trails for the

students and provides much-needed resources for psychology

teachers.

At the start of 2005, At-Bristol launched a brand new facility, The

Science Learning Centre South West supported by The

Wellcome Trust and The Department for Education and Skills. This

innovative initiative has created nine regional centres and a national

centre where qualified science teachers and technicians can rekindle

their excitement for science and update their subject

knowledge and skills. The centre has been created in collaboration

with The Universities of Bristol and Plymouth and At-Bristol is the

only science centre in the UK selected as the lead partner in the

development of a new Science Learning Centre.

As part of the programme for this new and exciting centre we shall

be creating courses for teachers on neuroscience with the aim of

increasing the amount of neuroscience being taught in schools.

And we shall be posing the question…that perhaps the time has

come to introduce neuroscience as an A’ level?

For more information: www.at-bristol.org.uk

By Penny Fidler (penny.fidler@at-bristol.org.uk)

16


Engaging scientists with the public

Greater emphasis is being

placed on communicating

science to the public, but how

can scientists fit such activities

into their already extremely

busy lives? Researchers Ellen

Poliakoff and Stuart Allan have

teamed up with science

communicator and filmmaker,

Erinma Ochu, to address the

issues and present some

solutions to engaging in science

communication and removing

the barriers to widening public

participation and interest in

science.

Erinma Ochu, Stuart Allan and Ellen Poliakoff.

If you’re at a party and get talking to a stranger and they ask you

what you do for a living, what do you say? Do you tell them that

you’re a scientist? And how much do you tell them about your

research? As Stuart Allan says, "One of the hardest things to do is

to explain to my friends or family what it is I do at work."

There is a wide mistrust and misunderstanding of science and what

scientists actually do, with scientists often being viewed as

eccentric, indulgent and coldly rational. As well as having personal

reasons to dispel these myths by communicating aspects of

science and scientific research to the public (and indeed our friends

and family), we have a professional obligation, with most research

being publicly funded. Indeed, most grant application forms now

include a small but significant

section about how the proposed

research will be disseminated to

the general public with grant

holders expected to engage in

activities to increase the awareness of science amongst lay

audiences. Furthermore, it is important to encourage more

students to consider studying scientific subjects at university,

especially at a time when the uptake of science subjects at school

is at an all-time low.

Two years ago there was a science communication event at the

BNA meeting in Harrogate chaired by Colin Blakemore, in which

Robert Winston spoke and Erinma Ochu showed a film about the

language barriers to dialogue between scientists and the public.

The 300-plus audience enjoyed the event, but the majority,

although interested, said that they simply do not have the time to

communicate science to the public. As Ellen Poliakoff explains "I

have been organizing events for Brain Awareness week for several

years and I find the events incredibly rewarding and enjoyable – the

enthusiasm and interest is infectious. On the other hand, I was

slightly nervous of getting involved again this year purely because

of the amount of time involved. But the starting point of the

discussions with Stuart and Erinma was how to tackle that very

problem."

Some of you may already be thinking about public communication

events and activities that you are already doing. There is another

common pitfall here. According to Erinma "There are many different

people across the university and, indeed, the country running fun

and exciting events, yet nobody knows what anyone else is up to.

Expertise is not shared and people often end up trying to re-invent

the wheel or using the simplest of practical activities. And at the end

of each project, there is no legacy so knowledge and resource

materials just disappear." And the

lack of time just exacerbates this

– someone might have just

enough time to run a one-off

event, but no time to write it up,

evaluate it or pass it on.

And how much do we know about

what the public want from us?

They are rarely consulted about

what activities they would like to

see, or what would be most

interesting or relevant for them,

although, increasingly, there is a

drive by those who fund science

communication activities to

promote partnership-working. As

Ellen comments "When we plan for events, we try to guess what the

children will find most interesting, but we’ve learnt from experience

that we often get it wrong - they may find the activity that we put in

at the last minute far more fun than a more complex one that we

spent weeks planning and that we thought was highly exciting."

So how can scientists with little or no spare time take part in public

engagement? And how can we share best practice and leave a

legacy? Furthermore, how can we involve and engage our target

audience when devising events so that there is genuine dialogue

and interaction? We are currently embarking on a series of projects

at Manchester, which we hope will address these issues. Indeed,

this very article is a first step in sharing our approach and ideas!

We are planning several projects

with activities that scientists can

take part in with minimal time

investment on their part and

with minimal disruption to their

working day. Furthermore, these projects will all leave usable end

products. The first, ‘A day in the life’, will involve giving a range of

scientists a disposable camera to record a typical or exceptional

day in their working life. They might be jetting off to an international

conference in Hawaii or stuck in a lab counting cells. The key will

be to presenting the many different activities and events that

encapsulates scientific life and research. The photographs will be

exhibited with the aim of showing some of the reality and variety of

how research is done and the human side of science – the coffee

with a colleague as well as the precisely timed experiment.

"One of the hardest things to do is to explain to

my friends or family what it is I do at work."

Erinma will be producing a documentary film project, ‘Why

Science?’, to explore the many and, hopefully, varied reasons that

different people chose to become scientists. Did they only choose

biology because the lectures started later in the day? Or did they

always know that they would end up working with fruit flies? Erinma

hopes that "...the film will connect with young people who are or

should be thinking about their future careers and the possibilities

that a career in science might present to them". The interviews for

the film will be scheduled around the scientists’ availability.

Another way of approaching the ‘lack of time’ issue is to involve

people at all levels of research. In ‘How Science?’, school pupils

will be mentored during their half-term holiday in a laboratory at the

University. They will spend time with staff at all levels, secretary,

technician, postgraduate, postdoc, lecturer and professor. Thus,

they will be exposed to many aspects of research life and a variety

of possible career options. During their visit, they will keep a video

diary which can be presented to their class the following term to

relate their experiences and help promote discussion. In addition,

17


SCIENCE AND COMMUNICATION

there are keen undergraduate students wishing to build up their

CVs. As Stuart highlights, "Each year we have a poster competition

between first year undergraduate tutorial groups and I am always

amazed at their creativity. We need to tap into this…" We will invite

undergraduates to participate in this year’s Brain Awareness Week

events. Furthermore, this area forms an ideal basis for an

undergraduate final year research project as we can involve

undergraduates in assessing the impact and outcomes of several

of our projects.

We will also be piloting the novel ‘public as communicators’

scheme for this year’s Brain Awareness Week (funded by a BBSRC,

MRC, NERC Small Grant Award for Public Engagement). Here, we

turn the idea of communicating science to the public on its head by

inviting a group of school children to actually help us devise and

run activities at the Manchester Museum to interest other members

of the public. A group of students, post-docs and lecturers will visit

the school to brainstorm ideas. Thus, preparing for the event

becomes a public engagement activity in its own right and we have

the benefit of a fresh approach to devising activities and materials.

We also hope that interesting scenarios will arise, such as a

knowledgeable 15-year-old showing a lecturer how to run an

activity on the day!

The group would also like to hear from you:

● Are you already involved in public communication?

● Do you have any questions or suggestions?

● Are you interested in taking part or sharing ideas?

● Or would you like to hear more about what we are doing?

Contact: Erinma.Ochu@manchester.ac.uk

The projects are supported by a Wellcome Trust Value in People

award from the University of Manchester and the Brain Awareness

Project is supported by a BBSRC, MRC, NERC Small Grant Award.

Neuroscience for kids: a personal ambition

ERIC H. CHUDLER is a Research Associate Professor within the

Department of Anaesthesiology at the University of Washington. His

main research interests focus on the cortical and basal ganglia

mechanisms of nociception and pain. He is also a committed educator

and communicator working with a number of organisations to promote

science and health education. He has made many public appearances

to this end and has published articles highlighting the importance of

scientists contributing to education and public scientific literacy.

Allowing young people access to the world of neuroscience is

something that Professor Chudler has personally taken to new levels.

Eric Chudler is responsible for setting up the website ‘Neuroscience

for Kids’. This colourful, interactive and in depth website covers a range

of areas from a basic, easy-to-follow introduction to brain structure to

articles about some of the latest published research findings. Victoria

Gill approached him to find out what led him to take such a pivotal role

in taking neuroscience to young people via the web. All the way from

Seattle and via email, he kindly agreed!

What is your academic background?

I graduated in 1980 from the University of California, Los Angeles

(UCLA) with a BSc in Psychobiology. During my first two years at UCLA,

I had planned to pursue a career in marine biology. However, during my

junior year, I volunteered to work in the laboratory of Dr. John

Liebeskind. Dr. Liebeskind encouraged me to go to graduate school. I

followed his advice and spent 1980-1985 at the University of

Washington. In 1983, I received an MSc in Psychology and, in 1985, my

PhD (also in Psychology). I then travelled to the east coast where I spent

my postdoctoral fellowship (1986-1989) at the National Institute of

Dental Research (National Institutes of Health) in the laboratories of Drs.

Ronald Dubner and Dan Kenshalo. After my postdoctoral fellowship, I

moved to Boston, MA, to work in the Department of Neurosurgery at

Massachusetts General Hospital. I travelled back to Seattle and the

University of Washington to work with Dr. Willie Dong as a research

assistant professor in the Department of Anesthesiology. In 1998, I was

promoted to my current position as a research associate professor.

What role do you think neuroscience has in elementary

education?

In most elementary schools, students begin to learn about the workings

of the human body. Neuroscience offers students and teachers the

opportunity to explore a wide range of topics including mental health,

drug abuse, neurological illness, anatomy and physiology, and ethical

and moral issues. Neuroscience "literacy" may help students

understand these subjects and to make better decisions about

problems that they may encounter in their lives.

Do you hope to update didactic science teaching methods in

order to interest children in science from a younger age?

I take my cues about teaching methods from classroom teachers and

other educators who study pedagogy. For example, I attempt to create

interactive, inquiry-based activities for young students make

discoveries by themselves.

What inspired you to launch the website and what is its ultimate aim?

Several years ago, my daughter’s kindergarten teacher invited me to

give a classroom presentation about the brain. I needed to develop

materials to keep the attention of 20 very young students. As I

developed these materials, I kept a record of the activities and noted

what worked and what did not. As my daughter progressed through

elementary school (she is now in 7th grade), I continued to make

presentations in her classrooms.

In 1996, Dr. Keith Kajander, a neuroscientist who I knew from my postdoctoral

times at NIH, visited me in Seattle. He told me about NIH

Science Education Partnership Awards (SEPA), a new NIH program to

fund science education projects. I applied for a SEPA grant to work with

neuroscientists and educators to develop a neuroscience resource for

the Internet and, in 1997, ‘Neuroscience for Kids’ was born.

Do you feel that dedicating yourself to public education leaves

you less time than you would like for your own research?

Certainly working in public education takes time away from bench

science. However, I believe it is essential that scientists give something

back to their communities, especially when their work is funded by

the public.

Do you think that all scientists should take on a role in the

educational process in order to improve scientific literacy amongst

the general public and how do you hope to see this role develop?

Absolutely! Scientists are a critical source of information. They are the

experts. Scientists can provide the public with information about what,

how and why they do their research. By interacting with the public

directly, this information will be unfiltered by the media or other sources.

Unfortunately, not all scientists are properly skilled in speaking with the

public, nor are all scientists comfortable speaking with young student

groups or the public. I would like to see programs that teach scientists

ways to interact with public and provide opportunities to these

scientists to engage the public.

Scientists can work independently to create their own opportunities to

work with the public. This can be as simple as a visit to their local

school. Many professional organizations can assist scientists interested

in public education. For example, the Society for Neuroscience assists

neuroscientists interested in outreach by providing teaching workshops

at the annual meeting and distributing materials to support classroom

presentations. A great opportunity for neuroscientists interested in

working with their communities is to participate in Brain Awareness

Week (March 14-20, 2005; March 13 – 19, 2006).

Professor Chudler’s website ‘Neuroscience for Kids’ is at

http://faculty.washington.edu/chudler/neurok.html

18


SCIENCE AND THE MEDIA

When Science Meets the Media

The Science Media Centre (SMC), as its name suggests, sits slap bang in the middle of ‘science’ and ‘the media’.

This is not always the easiest place to occupy. Scientists and journalists can be, and often have been, described as

being poles apart. The two disciplines seem to differ in virtually every possible way: from the timescales they work to

(decades versus hours), the way they think (uncertainties versus a need for absolute answers), to the context they put

this in (the ‘hows’ versus the ‘whys’). And these differences can often lead to a particularly fraught relationship

between the two.

Yet, despite this, many scientists are beginning to wake up to the

fact that they cannot ignore the media, especially after seeing the

consequences of the media furores around GM or MMR. And, in

fact, the very existence of the Science Media Centre is a result of

this abrupt change in attitude.

The Science Media Centre (SMC) was set up with the aim of

improving relations between these two disparate groups after the

House of Lords Report on Science and Society, published in 2000,

identified this as a key area to focus on to begin the rebuilding of

public trust in science and scientists. We have a specific focus here

on science in the headlines - think GM, MMR, cloning – as this is,

arguably, the time when the public is the most interested in, and

concerned with, science. For example, when a story about mobile

phone masts is on the front page of The Mirror, many readers

become very interested indeed in this area of science. It is our aim

to ensure that the news media, and, through them, the public, have

access to great scientists and, in particular, evidence-based

science at these crucial times.

The SMC has now been open for three years, and, in that time, has

been able to make a significant contribution to shaping how

science news has been reported. This has been both through

reactive work, such as ensuring that the media knows which

scientists are willing to comment and give up some of their time for

interviews when science is dominating the news agenda; and also

through proactive work, such as facilitating scientists to brief

journalists on new areas of science likely to hit the headlines. This

thereby ensures that their voices, views and opinions are heard at

these key times. As a centre set up by the scientific community, our

philosophy is that, if the media is to do science better, science

needs to do the media better.

When scientists roll up their sleeves and get stuck in with the

media, it can really make a difference to the way a story is covered.

For instance, when a recent stem cell breakthrough was reported,

by ensuring that scientists were on hand to comment on why this

research was being done, where it could lead, and what were the

ethical issues, it meant that the public also access these opinions

immediately, rather than solely the ‘slippery slope’ that science was

leading us onto. Similarly, when scientists briefed journalists about

nanotechnology at the SMC, they were primed and ready to cope

with Prince Charles’ ‘Grey Goo’ comments in the headlines.

The SMC would not be able to carry out any of this work without

hundreds of scientists, working for academia, government or

industry, who have given their time and expertise when science is

in the headlines. As science continues to advance at a rapid pace,

bringing exciting and, often, controversial new challenges, many

scientists are realising that they can no longer afford to remain in

their ivory towers, ignoring an ever-increasing media appetite. Yet

working with the news media need not be a painful experience. In

fact, in can actually be (dare I whisper the words) rather rewarding.

We want to help scientists see that the media can be an

opportunity rather than a threat. Science and the media may not fit

comfortably together, but public support for science will only come

when these two become happy bedfellows.

By Becky Morelle, Senior Press Officer at the Science Media

Centre.

If you are interested in finding out more about the Science Media

Centre, or about becoming an expert for us, then please visit our

website: www.sciencemediacentre.org or email Rebecca Morelle

(bmorelle@ri.ac.uk).

19


MEETING REPORTS MEETING

Report of the Society for Medicines Research Symposium

CNS Drug Discovery:

Challenges and Solutions

9 September 2004, London, UK

Mohammad S Alavijeh, F. Anne Stephenson & Alan M Palmer

The World Health Organization predicts that CNS disorders will become

the major medical need of the 21st Century. There are two major drivers:

first, the incidence of many CNS disorders, such as Alzheimer’s disease,

stroke and Parkinson’s disease, increase exponentially after age 65; and,

second, the number of people in the world over 65 is about to increase

sharply because of a marked rise in fertility after the Second World War.

However, it takes longer to get to a CNS drug to market (12-15 years)

compared to a non-CNS drug (10-12 years) and the attrition is higher. The

underlying reasons were the focus of this Society for Medicines Research

symposium, which was organized by Alan M. Palmer (Pharmidex, London,

UK) and F. Anne Stephenson (School of Pharmacy, University of London,

UK). More than 100 delegates heard an insightful review of the challenges

facing CNS R&D, along with a variety of innovative solution strategies.

Paul Whiting (MSD, UK) described how

CNS drug discovery began in 1951 with

the discovery that chlorpromazine

caused a ‘beatific quietude’, which led

to its use in calming agitated patients.

Clear-cut benefits were observed in a

variety of patients, including manics

and schizophrenics. The underlying

biochemical basis was subsequently

shown to be blockade of dopamine

receptors. This led to improved

compounds and to the birth of

neuroleptic drugs. However, there were

limitations: 1) they are not always

effective, 2) positive psychopathological

symptoms may benefit more

than negative, or deficit symptoms and

3) anti-psychotics are generally

associated with a variety of adverse

neurological effects. A major advance in

this area emerged in 1988 with the

emergence of clozapine, which had a

much reduced propensity to induce

adverse neurological effects. This was

the vanguard of a new generation of

"atypical" anti-psychotics.

The approach of discovering drugs on

the basis of behavioural changes in

experimental animals is much less

common today, largely because of the

emergence of developing drugs on the

basis of understanding disease

pathophysiology. This approach was

pioneered by post-mortem neurochemical

studies of Parkinson's

disease, where reduced concentrations

of dopamine and its major metabolite

(homovanillic acid) were observed in the

striatum. This loss was found to

correlate with both cell loss from the

substantia nigra and two of the three

cardinal symptoms of Parkinson's

disease (akinesia and tremor). This laid

the basis for replacement therapy – not

with dopamine (which does not cross

the blood-brain barrier), but with its

precursor: L-dihydroxyphenylalanine (L-

DOPA). This stimulated a number of

other groups across the world to begin

to investigate the biochemical basis of

other neurodegenerative diseases. A

clear consequence of this effort came

from three independent groups in the

UK who demonstrated that the activity

of the enzyme responsible for the

synthesis of acetylcholine, choline

acetyltransferase (ChAT), was reduced

in Alzheimer’s disease. It rapidly led to

the hypothesis that the dementia

associated with Alzheimer’s disease

occurs as a consequence of

dysfunction of cholinergic neurons,

which established the conceptual

framework for the emergence of

therapies to enhance cholinergic

function.

More than twenty five years later,

inhibitors of the enzyme responsible for

acetylcholine catabolism, acetylcholinesterase

(AChE), have become

the most successful approach, with

three such compounds (donepezil,

rivastigmine, and galantamine) now on

the market for the symptomatic

treatment of mild and moderate

Alzheimer's disease. These compounds

have a much better side-effect profile

than the first generation of AChE

inhibitors (physostigmine and tacrine).

Like other neurological disorders,

Alzheimer’s disease has a characteristic

neuropathology associated with

selective loss of neurones. Over the

past thirty years or so, brain research

has presented a number of drug targets

for the treatment of neurological

disorders. By contrast, psychiatric

diseases are much less tractable since

there are no characteristic brain lesions,

the biological basis is much less clear,

the genetics are more complex and

differential diagnosis is more

ambiguous.

There are many challenges in the

process of discovering and developing

new CNS medicines. These include:1)

the blood-brain barrier, 2) patient

heterogeneity, 3) multiple molecular

targets, 4) the predictive validity of

experimental efficacy models, 5)

establishing clinical proof of concept

and 5) establishing biomarkers of

disease existence or disease

progression.

1. The blood-brain barrier

The blood-brain barrier (BBB) is the

tight seal of cells that lines the blood

vessels in the brain and thus constitutes

a pivotal challenge to CNS drug

discovery: crossing this barrier to

interact with its molecular target is a

necessary prerequisite for all CNS

drugs.

Most small molecules and, essentially,

all peptides and proteins do not cross

20


REPORTS MEETING REPORTS

the BBB. Joan Abbott (King’s College

London, UK) reviewed both in vivo and

in vitro approaches to assess brain

penetration. The major in vivo model

she focussed on was in situ perfusion,

which measures the rate of entry across

brain endothelium. A shortcoming of

this approach is that it does not provide

a full pharmacokinetic profile (i.e.

maximal concentration, half life and

total exposure) and it does not take

account of egress mechanisms (e.g. via

P-glycoprotein). CSF concentrations

probably give a better measure of free

drug concentrations in brain, but Peter

Eddershaw (GSK, UK) argued that the

key compartment for a CNS active

compound is brain interstitial fluid,

which can be assessed by tissue

microdialysis.

There are in vitro models of BBB

function, including primary cultures of

endothelial cells. However, the

transendothelial electrical resistance

(TEER) of such cells is low (2000 Ωcm 2 . Since

the transmembrane resistance of

Madin-Darby canine kidney (MDCK)

cells are high (because of their tight

junctions), they are being used

increasingly in CNS drug discovery.

Eddershaw described how MDCK cells

transfected with human Pgp is used

routinely at GSK and other

pharmaceutical companies. This

system permits assessment of both

passive diffusion and active egress (via

P-glycoprotein).in a single assay

system.

2. Patient heterogeneity

This was clearly illustrated by a Chas

Bountra’s (GSK, UK) review of the

progress and pitfalls associated with

the discovery and development of new

medicines for the treatment of pain.

There are many types of pain: acute,

chronic inflammatory, chronic

neuropathic, chronic visceral pain,

headache and cancer. The type, nature,

duration and severity of the pain

associated with these conditions shows

great variation, reflecting heterogeneity

in the underlying pathophysiology.

Neuropathic pain has become a

particular target for drug discovery over

recent years, largely because it

represents a major unmet medical need.

3. Multiple molecular targets

There are many molecular targets for

any CNS disorder, but which one is

best?. To illustrate this Bountra

considered neuropathic pain in detail.

There are many targets, including:

a) NK1 receptors. Although NK1

antagonists showed clear efficacy in a

number of pre-clinical models of

neuropathic pain, they were ineffective

in the clinic. Does this mean that NK1

receptors are not a good target or does

it mean that the animal models have

poor predictive validity? It is also

possible that the compounds used had

insufficient brain and spinal cord

exposure.

b) Sodium channels: Sodium channels

are essential for neurotransmission and

are considered to play a role in the

plastic changes associated with

neuropathic pain. Knock outs of two

‘Considerable progress has

been made in understanding

the physiological, anatomical,

cellular, biochemical and

molecular basis of CNS

disorders. The challenge is to

translate this knowledge into safe

and effective new medicines’.

sodium channels (SNS and SNS2)

indicated the involvement of SNS (but

not SNS2) in development/maintenance

of neuropathic pain.

c) Vanilloid receptors: The transient

receptor potential cation channel V1

(TRPV1) is expressed in peripheral

nociceptive neurons and is subject to

polymodal activation via various agents

including capsaicin, noxious heat and

low extracellular pH. TRPV1 knock-out

animals show reduced responses to

jejunal mechanical and chemical stimuli.

This suggests that TRPV1 antagonists

will have utility in the treatment of pain.

d) P2X7 channels: This is the latest

member of a superfamily of ATP-gated

non-selective cation channels, which

are found on mast cells, microglia,

macrophages, Schwann cells and

endothelial cells. Their activation is

associated with release of mature,

biologically active interleukin-1b. P2X7

channels are up-regulated in DRG

following nerve injury, and knock-out

animals are resistant to the

development of inflammatory and

neuropathic hypersensitivity, suggesting

a role in initiating and / or maintaining

chronic pain.

4. The predictive validity of

experimental efficacy data

Predicting that a compound will be

effective in the clinic on the basis of preclinical

data is a major challenge for

CNS drug discovery. The throughput of

in vivo models is low so there is a need

for reliable in vitro models of CNS

disorders with good predictive validity .

Lars Sundstrom (Capsant, UK)

described a new generation of in vitro

models based on organotypic cultures

of slices of rat brain. New models have

been developed for disorders

associated with both acute (e.g. stroke

and traumatic brain injury) and chronic

(e.g. Alzheimer’s disease) neurodegenerative

disorders.

The profile of neuroprotection observed

in the organotypic cultures was very

similar to that seen with in vivo models

of stroke. However, the predictive value

of these models is not clear since the

efficacy observed pre-clinically with

NMDA and AMPA/kainate receptor

antagonists was not reproduced in

clinical trials. Similarly, the predictive

validity of experimental models of

neuropathic pain has been questioned

because NK1 receptor antagonists,

which showed efficacy in pre-clinical

studies, were found to be ineffective in

the clinic.

Thomas Rosahl (MSD, UK) presented a

powerful approach to drug discovery

that linked molecular structure to

behaviour. He illustrated this by a

description of GABA-A receptor

subtypes as targets for CNS disorders

such as anxiety, pain, Alzheimer’s

disease and epilepsy. Benzodiazepines

are the first line treatment for most

anxiety disorders, but,alongside their

beneficial anxiolytic, muscle relaxant

and anticonvulsant effects, they also

have several undesirable side-effects,

including an interaction with ethanol,

memory impairment, and a propensity

to cause tolerance and dependence.

They also have potential abuse liability.

The GABA-A receptor contains multiple

21


MEETING REPORTS MEETING

subunits, so there are many possible

permutations, the most common of

which are: α1βγ2, α2βγ2, α3βγ2 and

α5βγ2. Knowledge that the benzodiazepine

binding site is formed by a

and g2 subunits raised the possibility

that the desirable and undesirable

actions of benzodiazepines could be

separated. Rosahl described the use of

knock-in mice carrying benzodiazepine

binding site alterations to dissect out

the various effects of benzodiazepines

on individual GABA-A receptor

subtypes. The resultant data supported

the development of receptor subtypeselective

benzodiazepines with similar

anxiolytic properties, but with an

improved side-effect profile, when

compared to the current generation of

benzodiazepine drugs.

5. Establishing biomarkers of

disease existence or disease

progression

Getting a new medicine to market is

both costly and time consuming.

Vincenzo Libri (Lilly, UK) described how

a typical CNS drug discovery program

takes 13-16 years to get a compound to

market and, typically, costs $800-1000

million. In terms of process, it involves

the synthesis and screening of, maybe,

12,000 compounds, 80 of which are

then screened in detail, 10 of which are

assessed in humans with four involved

in full clinical trials and, finally, one

compound making it to market.

Approaches to increase the probability

of success and reduce expenditure are,

therefore, highly desirable.

Libri described how biomarkers have

the potential of making a large

contribution to CNS R&D. A biomarker

can be defined as a laboratory or a

physical sign used as a substitute for a

clinically meaningful endpoint; changes

induced by a therapy on a marker

endpoint can be expected to reflect

changes in a clinically meaningful

endpoint. While marker endpoints may

not be the true predictor of a genuine

clinical efficacy, they may provide initial

indication on whether the intervention is

sufficiently promising to justify the

conduct of larger-scale, longer-term

and more expensive clinical trials.

Biomarkers should be straightforward

to use, generate reproducible and

reliable results, correlate with disease

pathophysiology (a disease-based

surrogate marker), or be linked to the

mechanism of action of a potential new

therapy, and therefore be of use in

determining central penetration and/or

optimal dose (a mechanism-based

marker, or biomarker). Either way, the

relation between marker endpoint and

intervention should have a biological

relevance. Biomarkers can also help

improve diagnosis accuracy, reduce the

sample size, duration, and cost of

clinical trials and allow treatments to be

assessed in situations where the use of

primary outcomes would be

excessively invasive, unethical, long,

and/or expensive.

There are very few good biomarkers of

CNS disorders. A process of validation,

using both experimental animals and

humans, is now needed. This will

establish whether marker endpoints

actually support ‘Go/No Go’ decisions

at early stages of CNS drug

development. Validated biomarkers are

needed for most (if not all) CNS

disorders, but they are particularly

needed for clinical trials for chronic

neurodegenerative disorders, such as

Alzheimer’s disease and Parkinson’s

disease, where disease-modifying

therapies are now a distinct possibility.

Steve Williams (King’s College London,

UK) described the contribution that

neuroimaging has made to CNS drug

discovery. Positron Emission

Tomography (PET) and Magnetic

Resonance Imaging (MRI) constitute

the cornerstones of brain imaging and

they are both playing an increasingly

important role in CNS R&D. In recent

clinical trials, these modalities have

been used not only to refine subject

inclusion/exclusion criteria but also to

evaluate whether a drug has reached

the target organ and whether it has

produced the desired biological effect.

In relation to drug discovery, the

development of biomarkers is a key

goal of neuroimaging research. With a

focus on MRI imaging, he described

recent examples where imaging has

helped to expedite "go" or "no go"

decisions for several putative therapies.

These included the use of T2-weighted

MRI in multiple sclerosis, which was

used to expedite the approval of

betaseron by the FDA. It has also been

used to ‘visualise’: 1) tissue atrophy in

Alzheimer’s disease by, for example,

determining the total volume of CSF,

and 2) the evolution of neurodegenerative

changes in patients

following a stroke.

An approach that has great potential

utility is functional MRI, which takes

advantage of the differential signals

from deoxyHb and oxyHb. DeoxyHb is

paramagnetic (reduced T2*) and Hb is

diamagnetic (increased T2*). An

increased signal corresponds with

increased neuronal activity. This

approach has been used to show brain

activation occurring as a consequence

of photic stimulation (visual cortex) and

somatic stimulation (somatosensory

cortex). It has also been used in studies

of neuropathic pain (noxious

oesophageal stimulation) and working

memory (which included the

development of a virtual Morris water

maze).

Conclusions

The need for CNS therapeutics remains

high and looks set to increase

substantially in the years ahead. To

meet this need, it will be necessary for

CNS drug discovery to become more

efficient and effective. This meeting

identified a number of the bottlenecks

associated with getting a new CNS drug

to market. Considerable progress has

been made in understanding the

physiological, anatomical, cellular, biochemical

and molecular basis of CNS

disorders. The challenge is to translate

this knowledge into safe and effective

new medicines.

The Society for Medicines Research

(SMR) hold four ‘one day’ symposia

annually, some of which have a CNS

focus and student bursaries are

available. For further information:

A webcast of the meeting can be

found at: www.prous.com/cns

The SMR website is:

www.smr.org.uk

The Pharmidex website is:

www.pharmidex.com

22


REPORTS MEETING REPORTS

2nd Annual Meeting of

Southampton Neurosciences

Group: SoNG

September 23rd, 2004, University of Southampton

As a follow-up to the last issue of the BNA Bulletin (issue 49) that gave a

fascinating insight into neuroscience in Southampton, Lindy Holden-Dye

and Hugh Perry describe their September annual meeting of SoNG. It

brought together members with diverse but overlapping interests for a

lively day of debate, sharing ideas and socialising. There were over one

hundred delegates with contributions from the School of Medicine,

Psychology, Biological Sciences, Nursing and Midwifery and Health

Professions and Rehabilitation Services. The talks centred on the theme

of cross-cutting research activities, from basic to clinical neuroscience.

Some of the highlights are described below.

Dr Colm Cunningham, from Professor

Hugh Perry's group in the School of

Biological Sciences, described progress

they have made in understanding the link

between systemic infection and cognitive

status. Their interest focuses on

intriguing evidence from their animal

model of neurodegeneration, the prion

infected mouse, that systemic infection

may exacerbate the process, and

ultimately behavioural consequences, of

degeneration in the brain (Perry, V.H.,

2004, Brain Behav Immun. 18:407-13).

Recently this group has received further

funding from the BBSRC's Integrative

Analysis of Brain and Behaviour Initiative

to support a collaborative project with

the Schools of Psychology and Medicine

to define the molecular basis of this in the

animal model, and to relate this to

humans.

James Nicoll, Professor of Neuropathology

in the School of Medicine,

continued the theme of neurodegeneration

by presenting his group's

data on their post-mortem analysis of the

brains of patients from the Elan

Pharmaceuticals b-amyloid vaccination

trial for Alzheimer's disease (Nicoll, J.A.

et al., 2003. Nature Medicine 9, 448-452).

The paucity of plaques in the brains of

patients who received the vaccine is truly

remarkable although the consequence of

this for the progression of the disease is

still unclear. In collaboration with Dr Clive

Holmes, Professor Nicoll reported that

funding has been received from the

Alzheimer's Disease Trust to follow up

the patients involved in the vaccination

trial, both in terms of cognitive function

and neuropathology, to try to provide

answers to some of the outstanding

questions.

Professor Edmund Sonuga-Barke then

presented the work of the Developmental

Brain and Behaviour Unit which is broadranging

and aims to study the

relationship between neural processes,

psychological function and atypical

development and to translate this

research into clinical practise. In

particular, he described the work of this

group on gene-environment interactions

in Attention Deficit Hyperactivity

Disorder. He also described a very

interesting project (in collaboration with

Professor Sir Michael Rutter) which is

following English-Romanian Adoptees to

assess the impact of early institutionbased

deprivation on long term outcome.

Professor Ann Ashburn of the School of

Health Professions and Rehabilitation

Services followed with a very thoughtprovoking

presentation that illustrated

how important basic neuroscience can

be in optimizing strategies for the

rehabilitation of patients who have

suffered a stroke. For example, what is

the optimum timing for treatment? This

requires information on the temporal and

dynamic aspects of neuronal plasticity

that underpin recovery. This dovetailed

exceptionally well with the closing

lecture, 'Promoting axon regeneration

and plasticity in the damaged nervous

system', given by the invited lecturer

Professor James Fawcett from the MRC

Brain Repair Unit, Cambridge. This

provided an excellent overview of the

factors that may limit neuronal repair, but

described how even a small level of

regeneration could perhaps lead to a

marked improvement in the quality of life

for the patient. Professor Fawcett

focused on the role of proteoglycans

which are expressed in response to

neuronal injury, forming a perineuronal

net that is implicated in the inhibition of

brain repair.

The poster session that accompanied the

meeting was well-supported with more

than forty contributions covering topics

from invertebrate neuroscience, to animal

models of brain trauma and studies on

stroke in children with sickle cell

anaemia. Thanks to the generous

support of the British Neuroscience

Association and the Society for

Experimental Biology, the SoNG

committee were able to award two cash

prizes for the best posters. The winner in

the BNA category was Sarah Bayless, a

post-graduate student in the School of

Psychology with Professor Jim

Stevenson, for her poster on 'Executive

Functions and Behaviour in School-age

Children Born Prematurely'. In the SEB

category, the winner was Sarah Young in

the School of Biological Sciences with Dr

Philip Newland and Dr David Shepherd

for her poster 'Does Larval Diet Influence

Adult Food Choice? Gustatory

Learning and Memory in Drosophila

melanogaster'.

Overall, the most exciting aspect of this

meeting was the enthusiastic discussion

between neurosurgeons, neuropathologists,

clinical psychologists, those

working in rehabilitation services, and

basic cellular and molecular

neuroscientists. This provides a great

forum for the two-way discussion that is

required if clinically important problems

are to be tackled by lab research, and if

lab research is to be translated into

clinical practise. It is therefore very

satisfying to see that the annual SoNG

meeting is now well established in the

calendar at Southampton.

23


MEETING REPORTS MEETING

Treating depression:

fifty years on, and still no progress?

This was the provocative question posed by Colin Hendrie as part of the

BNA’s "Controversial Issues in Neuroscience" series of lively debates

organised in partnership with the European Dana Alliance for the Brain,

and hosted on 29th September, 2004, at The Dana Centre adjacent to the

Science Museum in London. A packed audience heard Jim Hagan, from

GlaxoSmithKline and Lewis Wolpert, professor of biology at University

College, London, reply to the protagonist from completely different

perspectives. Jane Qiu formerly a post-doctoral researcher at King’s

College, London, and now Associate Editor of Nature Reviews

Neuroscience, was fortunate to be in the audience and describes for us

the proceedings that evening.

Depression is an illness of antiquity.

According to Hippocrates, melancholy

was one of the four ‘humours’, alongside

the sanguine, the choleric and the

phlegmatic. He used the word

melancholia 2,500 years ago to

characterise a disease based on his

theory of four humours that may seem

strangely familiar with the modern

diagnostic classification of the same

disease. In its early expression,

melancholy was both a temperament and

an illness, and associated with fear,

withdrawal and madness. Later, it was no

longer regarded as an inert depression or

mere idleness, but became "a unique and

divine gift", an inspiring quality of genius

and "the animal heaviness of a sad,

earthy temperament to the height of a

struggle with intellectual problems".

How far have we really travelled on the

path of understanding this pervasive and,

at times, destructive mental condition?

Despite a tenuous grasp on the workings

of the depressed mind, modern medicine

has done its wonders, or so some claim.

Antidepressants, first discovered 50

years ago, have been variously hailed by

some as ‘wonder drugs’ that can make

the world a happy place. The condition’s

global prevalence – an estimate of 1 in 10

people at any one time and 121 million

worldwide – has made ‘happy pills’ the

most widely prescribed drugs and

constitute an industry worth 17 billions of

dollars.

But that might change. In the past year,

major journals have published papers

questioning the drugs’ safety and

effectiveness. There are mounting

concerns about whether antidepressants

such as Serotax and Prozac – marketed

by GlaxoSmithKline and Eli Lilly,

‘….every new drug has been just

a slight variation of its

predecessors, in large part

because no one really knows

what depression is or what

causes it’.

respectively — can make some patients

agitated and suicidal. There are also

other pressing questions: should they be

used in children? Can they also treat the

so-called "social anxiety disorders"? Are

GPs prescribing far too many pills for

people who do not have a serious clinical

condition? Against this backdrop of

controversy and uncertainty, the BNA

and the European Dana Alliance for the

Brain hosted an event called "Treating

depression: fifty years on, and still no

progress?" as part of the series of

"Controversial Issues in Neuroscience"

debate at the Science Museum’s Dana

Centre.

The speakers included Colin Hendrie, a

psychologist at University of Leeds; Jim

Hagan of the Psychiatry Centre of

Excellence for Drug Discovery at

GlaxoSmithKline; and Lewis Wolpert, a

professor of biology at University

College, London, a depression sufferer

and the author of the highly acclaimed

book "Malignant sadness: the anatomy

of depression".

"There has been no actual progress since

the first antidepressant was discovered

50 years ago," said Dr Hendrie. The first

antidepressant drug, Iproniazid, was

initially tested to treat tuberculosis, but

the patients reported feeling happier and

more energetic. It is an inhibitor of

monoamine oxidases, enzymes that

break down a group of chemicals called

monoamines (such as serotonin,

dopamine and noradrenaline) that

transmit messages across nerve cells.

Though new drugs have kept springing

out of pharmaceutical pipelines, the

ground has never been shifted – they all

work, as the theory goes at least, by

raising the level of monoamines.

Dr Hendrie said that, on many analyses,

the current antidepressants did not prove

significantly better than placebo.

Pharmaceutical companies claim that

70-80% of patients respond to the

antidepressants, but Dr Hendrie thinks

that this figure is largely "overestimated".

And when the drugs do work, it takes 4–6

weeks to have an effect. "Patients often

feel worse before they feel better," he

said. "The effect of making already

suicidal people feel worse is a major

problem."

"The single major advance in depression

treatment in the past 50 years is to

reduce side-effects, so more people can

carry on taking them," he continued.

"This is rather disappointing if one

considers what kind of scientific progress

can be made during a 50-year period in

other areas." Indeed, aeronautics went

from the first powered flight by the Wright

brothers in 1903 to putting satellites into

space in 1953; and genetics went from

the discovery of the structure of DNA in

1953 to mapping out the entire human

genome in 2001.

24


REPORTS MEETING REPORTS

So what has gone wrong? Dr Hendrie

thinks that the current drug discovery

strategy for depression is fundamentally

"flawed". It mainly focuses on developing

new drugs, by replacing the nonessential

parts of existing ones, without

understanding the pathology of

depression or how the drugs actually

affect the depressed brain. For decades,

therefore, every new drug has been just a

slight variation of its predecessors, in

large part because no one really knows

what depression is or what causes it.

"All antidepressant development is

based on the monoamine hypothesis,

but there is virtually no evidence to

support it," remarked Dr Hendrie. At the

level of neurons, the drugs’ action is seen

within hours, but the full clinical effect

can take up to eight weeks. So it seems

‘It’s a strange state of mind — if

you can describe your

depression then you probably

haven’t got it’.

that the drugs may not produce the

antidepressant effect directly, and other

pieces of the puzzle remain to be

determined. "According to brain imaging

studies, there is a reduction in the blood

flow in the brains of depressed patients,"

Dr Hendrie continued. "And other studies

showed that various brain structures,

such as the hippocampus, were smaller

in people with a history of recurrent

depression." As 90% of the brain is made

up of glial cells, Dr Hendrie conjectured

that manipulating the glial cell function

might represent a new avenue for

effective treatment of depression.

Dr Hagan, however, was not impressed.

"Antidepressant drugs are effective in up

to 70% of the patients. They are now

safer and better tolerated," he said. Early

generations of antidepressants can

cause serious side effects, such as dry

mouth, constipation and irregular

heartbeat, and the risk of a fatal

overdose. Prozac and Seroxat are as

effective but without the side-effects.

"Improved side effects and tolerability

are important for compliance in

depression, and compliance partly

dictates responses," he continued. Good

tolerability has also allowed treatment of

patients with other conditions such as

anxiety, panic attacks, social anxiety

disorder, obsessive-compulsive disorder

and post-traumatic stress disorder.

He recognized that the neurobiology of

depression was poorly understood and

that the monoamine theory could not

fully explain the drugs’ antidepressant

effect. "Nevertheless, monoamines are

still important targets for treating

depression," he maintained. "It works,

and therapeutic advances can be built

most successfully (but not exclusively) on

what is known." A new trend in

antidepressant development is to

develop drugs that have multiple targets.

For example, Eli Lilly’s Cymbalta raises

levels of both serotonin and

noradrenaline; GlaxoSmithKline’s

Wellbutrin XL affects noradrenaline and

dopamine. The rationale is that, by

aiming at multiple receptors, the drugs

will be either faster or capture a larger

percent of responders.

"Monoamine targets constitute less than

half of the current pipeline research

programmes in the pharmaceutical

industry," added Dr Hagan. He explained

that another important target was

corticotrophin-releasing factor (CRF) – a

crucial factor in the brain that triggers the

release of the stress hormone cortisol.

The link between stress and depression

is well documented, and there are high

levels of cortisol in the plasma of patients

with depression. Nearly every major

company is now pursuing CRF

antagonists, which probably are the lead

alternative to available antidepressants.

Dr Hagan said there were many

obstacles to developing novel

therapeutic approaches in tackling

depression. The main issue is that there

are few animal models to test the

theories. Depression in humans is often

defined by arbitrary and subjective

symptoms rather than concrete

physiological measures. Whether

animals get depressed is arguably still

debatable. Thus, animal models can, at

their best, only reflect pieces of the

symptoms or behaviours remotely

resembling depression in humans. Other

obstacles include the lack of indicators of

the drug response and efficacy, the

placebo effect and the heterogeneity of

the condition.

Though there are many hurdles to

overcome, Dr Hagan is optimistic that

the pharmaceutical industry is able to

accept the challenges. "But progress

requires a coordinated research strategy

between pharmaceutical, academic,

clinical and neuroscience communities,"

he concluded.

After the head-to-head discussion on the

current situation of antidepressant

development, Professor Wolpert revealed

his own struggle with depression and the

attempt to understand this devastating

condition. Over ten years ago, clinical

depression hit him without any warning –

he had a successful scientific career and

a happy family life. "It is a strange state of

mind – if you can describe your

depression then you probably haven’t

got it," he said. He couldn’t think, let

alone work, and was suicidal.

When eventually recovered, through a

combination of psychotherapy, drug

treatment and support from friends and

family, Professor Wolpert went into an

extensive literature research on

depression – from the history of the

melancholy temperament to contemporary

neuroscience – which led to his

critically acclaimed book "Malignant

sadness: the anatomy of depression".

"What is the origin of depression? And

does it have an evolutionary adaptive

function?" he asked. According to Freud,

sadness is the emotion most close to

depression. "Thus depression may be

sadness become unhinged," suggested

Professor Wolpert. "Sadness is a basic

and universal emotion. Its function is to

promote attachment to people, things

and aims." Depressive feelings are

experienced by all people and are a

normal component of anxiety,

disappointment and grief. Therefore, they

may have adaptive functions. "People

reassess their lives during depression –

it’s just that 10% kill themselves as a

result," he said.

Professor Wolpert was concerned with

the stigma associated with depression

and people’s tendency to resist taking

antidepressants. He said depression was

just another illness, like cancer and gall

bladder disease, and there was nothing

to be ashamed of. "If we can talk about

gall bladder disease, why can’t we talk

about depression?" he asked. From his

experience, antidepressants worked but

he thought that the monoamine theory

was probably given too much credence

and other approaches, such as

psychotherapy and social support, were

important as well. "We should try to

understand depression in both scientific

and humane terms, and use a more

holistic approach to help those in its

grip," remarked Professor Wolpert.

25


MEETING REPORTS MEETING

At the end of the talks, a member of the

audience asked Dr Hagan whether

GlaxoSmithKline had any evidence that

Seroxat might cause self-harm and

suicidal thoughts in some patients,

especially children. In June 2004, the

state of New York filed a lawsuit against

GlaxoSmithKline, alleging that it

suppressed research results that linked

Seroxat to the suicide risk. This has

evoked mounting public upheaval and

media frenzies. But the answer from Dr

Hagan was a resolute "no". He said that

no evidence had suggested such a link

and that, in response to the public

concern, the company had publicised

the results of clinical trials on its website.

Dr Hendrie explained that severe

depression was often characterised by

suicidal impulses but most patients were

so lacking in energy and paralysed by

their illness – a condition dubbed

‘psychomotor retardation’ – that they

didn’t act on those impulses. But when

patients are treated with antidepressants,

different symptoms of the illness lift at

different rates: psychomotor retardation

is the first thing to go, while existential

sadness the last.

‘People reassess their lives

during depression — it’s just

that 10% kill themselves as

a result’.

Another member of the audience asked

whether GPs were prescribing far too

many antidepressants to people who do

not have a serious clinical condition.

Several million people are given the

drugs in Britain, including more than

50,000 children. "GPs know nothing

about depression," Professor Wolpert

was quick to answer. Dr Hendrie said that

"talking therapies" might be more

suitable with people with moderate

depression but these were in very short

supply and the NHS waiting time could

be in the order of months. "So popping a

pill is much easier," he said. But growing

concerns about the antidepressants’

safety issue and addictive nature may

change that. People might begin to think

twice before popping the pills, and

consider opting instead for psychotherapy.

This is not "cosmetic psychopharmacology"

after all.

Complicated problems never have simple

solutions, and depression–this intricate

and baffling human illness–is no exception.

Two and half millennia after Hippocrates’

first description of this mental condition,

the quest for answers goes on.

7th IBRO African School of

Neuroscience on Molecular

Neuropharmacology

Nairobi, Kenya, 1st – 8th November, 2004

Several members of the BNA contributed to the 7th IBRO School of

Neuroscience held at the International Centre for Insect Physiology &

Ecology, Nairobi, Kenya, between the 1st and 8th November, 2004. The

focus of the course was Molecular Neuropharmacology.

This advanced programme was

sponsored by the International Society

for Neurochemistry and IBRO. Generous

support was also provided by

GlaxoSmithKline (GSK), Axon

Instruments (now Molecular Devices

Corp.), the Department of Medical

Physiology, University of Nairobi and the

Society for Neuroscientists of Africa

(SONA).

The 21 students selected for this course

came from Zimbabwe, Kenya, Nigeria,

Uganda, Cameroon, Ethiopia and

Morocco. The invited faculty, with

specialist expertise in molecular

neuropharmacology, also arrived from far

and wide and were Dr Ataulfo Martinez-

Torres (Mexico), Drs Roger Butterworth

and Ante Padjen (Canada), Drs Robert

Halliwell and Leanne Coyne (USA), Drs

Raj Kalaria, Andrew Randall and Jon

Spencer (UK), Dr Laurie Kellaway (South

Africa), Dr William Wisden (Germany) and

Dr Nilesh Patel (Kenya).

The instructors gave an excellent series

of lectures each morning covering

several major areas of neuropharmacology,

including ion channels,

receptors, signaling, molecular neurobiology,

genomics, channelopathies,

microarrays and drug discovery.

Technical lectures were also given on

making electrophysiological recordings

from neurons, expressing recombinant

receptors in cells, mapping receptors in

the brain and making transgenic mice.

In the afternoon, a series of ambitious

laboratories ran and provided students

with a hands-on experience of isolating

brain RNA, preparing and injecting

Xenopus Laevis oocytes with RNA or

DNA; making two-electrode voltageclamp

recordings from the oocytes;

preparing a brain slice and recording,

extracellularly, field potentials from the

hippocampus, and inducing epileptiform

activity and Long-Term Potentiation (LTP)

in these preparations.

26


REPORTS MEETING REPORTS

Late into the evenings, a series of social

lectures were delivered on topics such as

the ‘history of the drug receptor’, ‘taste

and smell’ and ‘careers in Big Pharma’. In

addition, the students also appraised a

scientific article in a journal club meeting

and, at the end of the week, they each

gave a short presentation on a piece of

research they had conducted or on a

project they aimed to submit for grant

funding. Feedback from faculty and

students was given to all presenters.

This was a very full programme and the

students and instructors worked very

diligently. At the end of the course, each

student was provided with a CD to take

home containing all of the lecture and lab

materials for the entire course. In

addition, GSK very generously donated

the equipment used to make extracellular

recordings during the course to

IBRO for use in future neuroscience

schools.

The instructors and students also

enjoyed social activities together in the

evenings. Indeed, on the last night, a

dinner was held at the Safari Park hotel in

Nairobi where the non-squeamish, nonvegetarian

amongst the group were

treated to a meal of camel, zebra, ostrich,

gazelle, crocodile and assorted other

meats!

By Robert Halliwell and Nilesh Patel

THE CHRISTMAS SYMPOSIUM 2004

‘Windows on the Brain:

getting closer to the action’.

15th December, 2004, at The Royal Society, London

The steady stream of neuroscientists that filed into the Royal Society in London was testament to the broad

appeal of the theme of this year’s BNA Christmas Symposium, "Windows on the Brain", and to the quality of the

speakers assembled for the two sessions. As always, it proved to be a thoroughly enjoyable and enlightening

afternoon. For those unable to attend, Justin Boyes describes the afternoon’s events that concluded, as always,

with mince pies and a glass of wine (or two!). Justin is a Postdoctoral Research Fellow at Aston University,

Birmingham and a Visiting Fellow at the MRC Anatomical Neuropharmacology Unit, Oxford.

The first session, chaired by Deborah Dewar, got underway with

a presentation by Angus Silver (London) entitled "Focusing on

central synaptic mechanisms with new optical methods". The

first part of the talk detailed recent work on presynaptic calcium

dynamics and introduced us to the first of several state-of-theart

microscopic techniques covered during the symposium:

high-temporal-resolution spot-confocal microscopy. With this

technique, it is possible to measure fast calcium changes with

high spatial resolution, thus enabling the detection and

modelling of calcium gradients within individual axonal

boutons, in this case the cerebellar mossy fibre terminal. Dr

Silver then moved to the other side of the synapse and

described some of the kinetic properties of postsynaptic AMPA

receptors. The combination of patch-clamp recording from

granule cells in brain slices, and the localised un-caging of

glutamate (with UV illumination), permits the study of synaptic

AMPA receptors in a single postsynaptic density. This approach

demonstrated that the number of functional receptors is likely

to differ between synapses and that receptor occupancy is low.

Furthermore, the de-sensitisation of AMPA receptors in granule

cells is less than expected.

In the second presentation, Peter Somogyi (Oxford) posed the

question of how patterned pyramidal cell firing and stereotyped

network oscillations are generated in the cerebral cortex. He

began by outlining the great diversity of GABAergic

interneurons within the hippocampus, of which an impressive

17 distinct types are currently recognised. Focusing on two

classes of interneurons, defined by their expression of either

parvalbumin or cholecystokinin, he elegantly described the way

in which a detailed knowledge of the connections and firing

patterns of individual neurons can contribute to an

understanding of the role of a given neuronal population within

a network. Thus, interneurons innervating distinct functional

domains of CA1 pyramidal cells fire preferentially at different

times during network oscillations. This spatio-temporal diversity

suggests that, rather than simply providing generalised

inhibition, GABAergic inputs dynamically control the activity of

pyramidal cells.

The third presentation, given by Jeremy Henley (Bristol), was

intriguingly titled "The ins and outs of glutamate surface

expression". The talk covered several aspects of the

distribution and dynamics of AMPA receptors, studied in real

27


MEETING REPORTS MEETING

time in cultured hippocampal

neurons using green fluorescent

protein (GFP) technology and

confocal microscopy. Combining

this with fluorescence recovery

after photobleach (FRAP) to

investigate intracellular AMPA

receptor movement, Prof. Henley

demonstrated that GFP-GluR1 is

transported in dendrites at rates

comparable with fast axonal

transport and that AMPA receptors

move in a predominantly, but not

exclusively, proximal to distal

direction. He went on to describe

mutant, pH-dependent GFPs,

called pHluorins, which fluoresce

only when expressed on the cell

surface. This technique was used

to investigate changes in AMPA

receptor surface expression

following chemically induced LTD.

Perhaps surprisingly, the

internalisation of pHluorin-GluR2 that

followed NMDA application appeared to

occur preferentially at extrasynaptic sites

on dendrites and was followed by the

lateral diffusion of synaptic receptors.

A short tea break was followed by the

annual presentation of the BNA Awards.

This year’s award for ‘Public Service’ was

presented to the European Dana

Alliance for the Brain (EDAB) in

recognition of their outstanding work in

promoting public awareness of brain

research through Brain Awareness Week.

The award was gratefully received on

behalf of EDAB by Elaine Snell. The

award for ‘Outstanding Contribution to

British Neuroscience’ was presented to

Geoffrey Raisman, director of the newly

established Spinal Repair Unit at UCL,

for his pioneering work in stem cell

research, which has raised the possibility

that spinal cord injuries, long considered

incurable, could be repaired.

The second scientific session, chaired by

Richard Frackowiak, started with Dimitri

Kullmann (London), who presented a talk

entitled "A window on plasticity of

inhibition in the cortex". Prof. Kullmann

began by describing coincidence

detection in hippocampal pyramidal

cells. This mechanism may be important

for information processing in the cortex

because it allows timing to be maintained

across large networks of neurons.

However, the temporal discrimination of

synaptic inputs by CA1 pyramidal cells is

compromised by long-term potentiation

(LTP), which is puzzling given that LTP is

also thought to underlie memory

encoding. Crucially, Prof. Kullmann

demonstrated that approximately 40% of

GABAergic interneurons in the

neighbouring stratum radiatum, including

those that provide feed-forward inhibition

onto pyramidal cells, also display LTP.

Plasticity in these ‘LTP-competent’

interneurons was shown to be dependent

upon NMDA receptors that were tyrosine

phosphorylated by src-family kinases. He

then went on to provide strong evidence

that LTP in interneurons is sufficient to

rescue the temporal fidelity of

coincidence detection in pyramidal cells.

This was followed by the afternoon’s only

overseas speaker, Rosa Cossart

(Marseilles), who gave us a

comprehensive description of twophoton

calcium imaging, a powerful

technique for "watching thousands of

neurons at work". This technique allows

the real-time analyses of the activity of

large populations of neurons with singlecell

resolution, making it possible to

understand cells in the context of

the network in which they operate.

Furthermore, it offers significant

advantages over conventional

scanning microscopy, including

better penetration, less photobleaching

and less photodamage

to the cells. Recordings of calcium

transients in spontaneously active

neocortical slices revealed that

groups of neurons that display

synchronous activity are often

spatially arranged, with the peaks

of synchronous activity corresponding

to maximal organisation

of co-active cells. Dr Cossart then

showed data from patch-clamp

analyses of identified neurons,

demonstrating that synchrony

occurs when several neurons

simultaneously shift to membrane

potential UP states.

The afternoon ended with Michael

Hausser (London) addressing the

question of how neurons transform

synaptic inputs into outputs. Dr Hausser

began by presenting data from in vivo

patch-clamp recordings from cerebellar

granule cells. Although granule cells can

be driven to fire at high frequencies, their

spontaneous firing is very low, with

action potentials requiring the summation

of excitatory mossy fibre inputs. He went

on to demonstrate that this is a

consequence of tonic GABAergic

inhibition mediated by Golgi cells, which

reduces the excitability of the granule

cells, preventing response to mossy fibre

input. However, sensory input elicits

bursts of firing in granule cells, with an

approximately linear relationship

between mossy fibre input and granule

cell output, implying that mossy fibre

EPSPs must summate to evoke action

potentials in granule cells. Dr Hausser

finished by describing studies

investigating synaptic inputs to Purkinje

cells using two-photon calcium imaging,

which showed that climbing fibre inputs

initiate a global calcium signal in Purkinje

cell dendrites.

By Justin Boyes

(justin.boyes@pharmacology.oxford.ac.uk)

28


Biochemical Society Focused Meeting

22–23 September 2005

Chilworth Manor and University of Southampton, UK

M o le c u la r D e t e r m in a n t s o f S y n a p t ic

F u n c t io n : M o le c u le s a n d M o d e ls

Images kindly supplied by the University of Southampton and The School of Pharmacy, London, UK

The synapse represents a highly specialized sub-cellular compartment that has evolved to support the intricate signalling required for

brain function. In the last 20 years a myriad of synaptic molecules have been identified and this has been followed by an increasing

effort to understand their functional significance. This increased understanding of the biochemical mechanism (post-synaptic receptor

signalling, transmitter release mechanisms, synaptic maturation and death) has also promoted an investigation of these molecular

determinants in the context of cellular, systems and whole animal physiology. This meeting will provide an integrated view of current

and emerging concepts in our understanding of the molecular determinants of synaptic function. This will be achieved by a programme

of participating speakers who have used specific molecules, specific synapses and/or specific organisms to generate observations that

inform about the molecular basis of synaptic function. There will be a significant contribution from investigators using the established

major post-genomic vertebrate and invertebrate neurobiological model organisms (Mouse, C. elegans and Drosophila). In addition, the

meeting will consider how synaptic dysfunction might contribute to neurological disorders.

C o n f ir m e d

S p e a k e r s :

O r g a n iz e r s :

S p o n s o r s :

George Augustine (Duke, Durham, USA)

Heinrich Betz (MPIH, Frankfurt, Germany)

Mario de Bono (MRC-LMB, Cambridge, UK)

Kendal Broadie (Vanderbilt, TN, USA)

Nils Brose (MPIEM, G“ottingen, Germany)

Annette Dolphin (University College London, UK)

Seth Grant (Cambridge, UK)

Giovanni Lesa (University College London, UK)

Henry Markram (Brain & Mind Institute, Lausanne,

Switzerland)

Nigel Unwin (MRC-LMB, Cambridge, UK)

Andres Villu Maricq (Utah, USA)

Giampietro Schiavo (Cancer Research London, UK)

John Scott (HHMI/Vollum Institute, Portland, OR, USA)

David Shepherd (Southampton, UK)

Kang Shen (Stanford, CA, USA)

Vincent O’Connor (Southampton, UK)

Lindy Holden-Dye (Southampton, UK)

F. Anne Stephenson (London, UK)

BBSRC

Ferring Research Limited

GlaxoSmithKline

Merck Sharp & Dohme

Syngenta

The Gerald Kerkut Charitable Trust

Poster Abstract Deadline:

29 July 2005

Early Registration Deadline:

22 August 2005

P o s t e r P r iz e s :

Sponsored by

The Gerald Kerkut Charitable Trust

F e e s :

(include 2 nights accommodation, refreshments,

lunch and the meeting dinner)

Full member £300

Student £215

Non-member £400

Late fee

(charged after 22 August 2005) £50

Biochemical Society Transactions

Volume 34 Issue 1

(published transactions of the

meeting – of invited speakers only) £25

Registration and further details can

be found at www.biochemistry.org or

contact meetings@biochemistry.org


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NOTICE BOARD

Forthcoming meetings

of the Clinical

Neurosciences Section

Neurodegeneration

Thursday 14 April 2005

Speakers include:

Professor Chris Shaw, Professor Nick Wood

and Dr Angus Kennedy

Aspects of the neurological examination

Thursday 5 May 2005

Speakers include:

Dr Michael O’Brien, Dr Michael Donaghy

The past, present & future of neurosciences

Thursday 2 June 2005

For further information and registration form

please contact:

Mr Damian Fry

Academic Department, Royal Society of Medicine,

1 Wimpole Street, London W1G 0AE

Tel: (+44) (0) 20 7290 2984 Fax: (+44) (0) 20 7290 2989

Email: cns@rsm.ac.uk

For further details on these and other forthcoming

Section meetings at www.rsm.ac.uk/cns

Sensorimotor

systems and

movement control

A symposium to celebrate

the career and to mark

the retirement of

Professor David Armstrong

University of Bristol

24th of July 2005

Venue:

Department of Physiology, University of Bristol

Details:

http://meetings.physoc.org/bristol/symposia2407a.asp

or email r.bissett@bristol.ac.uk

May 12-15, 2005, Santorini, Greece

International meeting on

CORTICAL DEVELOPMENT:

NEURAL STEM CELLS TO NEURAL CIRCUITS

ORGANISERS:

Arnold Kriegstein and John Parnavelas

PROGRAMME COMMITTEE:

Fiona Doetsch, Gord Fishell (Chairman), Magdalena Götz, Arnold Kriegstein, John Parnavelas

SESSIONS INCLUDE:

neural stem and progenitor cells, arealization, migration, and neural subtype specification

FEATURED SPEAKERS:

Arturo Alvarez-Buylla, Stewart Anderson, Eva Anton, Colette Dehay, Fiona Doetsch, Gord Fishell, Joe Gleeson,

Magdalena Götz, Elizabeth Grove, Francois Guillemot, Corinne Houart, Zaal Kokaia, Ryoichiro Kageyama, Arnold

Kriegstein, Laura Lillien, Steve Noctor, Dennis O'Leary, Nancy Papalopulu, John Parnavelas, Franck Polleux,

Pasko Rakic, John Rubenstein, Austin Smith, Seong-Seng Tan, Li-Huei Tsai, Christopher Walsh, Hynek Wichterle.

FOR MORE INFORMATION, REGISTRATION AND TO SUBMIT ABSTRACTS FOR POSTER PRESENTATION PLEASE CONTACT:

Triaena Tours and Congress, Egnatias 75, 54635 Thessaloniki, Greece, Tel +30 2310 256-194/5, Fax +30 2310 256-

196, email salonica@triaenatours.gr See also: www.coorticaldevelopment.org

Registration is limited to the first 210 applicants.

31


NOTICE BOARD

Neurology for Neuroscientists (XI)

7-8 APRIL 2005 - MAGDALEN COLLEGE OXFORD

Sponsored by the Guarantors of Brain

This symposium is open to research workers in the field of neuroscience and aims to provide them with the

clinical background to neurological diseases, and with insights into how neurological problems

can illuminate basic neuroscience.

The course is limited to 60 participants. Course including 1 night accommodation / food - £350.

Application forms may be obtained from:

Professor JB Clark, Department of Neurochemistry, Institute of Neurology, Queen Square, London WC1N 3BG

Email: mailto: nneurosc@ion.ucl.ac.uk nneurosc@ion.ucl.ac.uk -

Tel: 020 7837 3611 ext 4201 - Fax 020 7833 1016

For further details and to download application forms please see our website:

http://www.ion.ucl.ac.uk/neurochemistry/n4n.html

Deadline 18th March 2005

VACANCIES VACANCIES

JOBSJOBSJOBSJOBSJOBS

Conway Institute of Biomolecular

& Biomedical Research,

University College Dublin

The Conway Institute of Biomolecular & Biomedical

Research, University College Dublin, invites applications

for 3-year PhD fellowships from eligible students

interested in the area of Molecular Neuroimmunology.

Neuroimmunology, the study of interactions between the

immune and the nervous systems, is a rapidly growing

area of research with enormous potential to contribute to

our understanding of physiological and disease

processes. This innovative research and training

programme will equip motivated graduates with the

appropriate expertise and skills required to excel in this

emerging area.

Further details and application forms available

on the following link:

http://www.ucd.ie/conway/postgraduate_mnest1.html

or by emailing mniest@ucd.ie

Closing date 30th April 2005

Institute of Physiology,

University of Bern

Ph. D. student position in Neurophysiology

Starting in April 2005, a pre-doctoral position is available in the

Neurophysiology group of the Institute of Physiology at the

University of Bern. The project aims to study the functionality of

layer V pyramidal cells of the somatosensory cortex during in

vivo - like conditions (Berger et al., J. Neurophysiol. (2001) 85:

855-868; Berger & Lüscher, Cereb. Cortex (2003) 13: 274-281;

Berger et al., J. Neurophysiol. (2003) 90: 2428-2437). Therefore

state of the art electrophysiology techniques like dendritic and

somatic whole-cell recordings as well as calcium imaging

techniques in acute slices will be used. Salary according to the

scale of the Swiss National Science Foundation. The position is

open for Swiss and EU citizens. Duration is three years.

Applicants with a MSc or similar degree in Biology or Physics

(practical experience in electrophysiology and / or imaging

techniques would be an advantage) are invited to send a letter of

motivation, CV, a short description of their previous work (topics

and techniques), and at least one reference to Dr. Thomas

Berger, Institute of Physiology, University of Bern, Bühlplatz 5,

CH-3012 Bern, Switzerland.

For further information call: +41 / 31 / 631 5257

Fax: +41 / 31 / 631 4611

E-mail: berger@pyl.unibe.ch

webpage: http://www.physio.unibe.ch/

32


VACANCIES VACANCIES

JOBSJOBSJOBSJOBSJOBS

Queen Mary, Barts and the London

University of London Queen

Mary's School of Medicine

and Dentistry

Research Assistant

Applications are invited for a Research Assistant position in the

Neuroscience Centre, within the Institute of Cell and Molecular

Science at St. Bartholomew's and the Royal London Hospital,

Queen Mary's School of Medicine and Dentistry, University of

London. The project is supported by a Heptagon Fund award and

involves in vitro and in vivo studies on the validation of new

compounds with therapeutic potential in Alzheimer's disease.

The study is carried out in collaboration with the Department of

Chemistry at Queen Mary, where the original compounds, that are

patent-protected, are synthesized.

The Neuroscience Centre encompasses the academic

departments of neuroscience, neurosurgery, neurology and

neuropathology. Its research focuses on trauma and

neurodegeneration and on strategies for neuroprotection and

neuroregeneration. The main laboratories are currently based at

Queen Mary College, the Mile End campus, and have excellent

whole animal, tissue culture, histology, and light and electron

microscopy facilities. In April 2005 the Centre is scheduled to

move into a new research centre, the Institute of Cell and

Molecular Science, at Whitechapel, on the Royal London Hospital

site, which will provide new laboratories and core facilities.

The Heptagon project is funded initially for 1 year. The position

would ideally suit a postgraduate student with a background in

Biology (preferably Biochemistry or Neuroscience) or

Pharmacology, who is considering a career in research. The

position gives the opportunity to gain research experience before

long-term commitment to a higher research degree. Experience

of specific techniques is not essential, as training will be given for

all the techniques used in the project.

Applicants should send their CV and the names of 2 referees in

an electronic format (e.g. Word file) to Dr. Adina Michael-Titus,

Neuroscience Centre (A.T.Michael-Titus@qmul.ac.uk). Informal

enquiries can be made to Dr. Michael -Titus (tel. 020-7882-6361).

The deadline for application is 1st June 2005. Interviews will be

held during June and the project will start immediately thereafter.

Department of Biological Sciences

University of Warwick

ATP and the central regulation

of breathing

Position available:

BBSRC PhD Studentship

Project Summary:

In mammals, PCO2 in arterial blood provides the major drive

for respiration. Central chemoreceptors within the ventral

medulla oblongata detect PCO2 and enhance ventilation if this

rises. Understanding these chemosensory mechanisms is one

of the big challenges of the respiratory field. We have recently

made a breakthrough by showing that ATP is rapidly released

from the chemosensors in vivo and constitutes an important

link in this chemosensory reflex.

This project will exploit the ATP microelectrode biosensors that

we have invented at Warwick to identify the chemosensitive

cells and investigate in greater depth the mechanisms of ATP

release. The biosensor recordings will be combined with

standard patch clamping methods, in situ hybridization to

localize ion channels and ecto-ATPases in the ventral medulla,

and cell dissociation techniques. Ultimately this project will

identify the ATP-releasing chemosensitive cells, their location,

the mechanisms of CO2 chemosensory transduction and their

relationship to the control of respiration.

Spyer KM et al (2004) ATP is a key mediator of central and

peripheral chemosensory transduction. Exp Physiol 89, 53-59.

Gourine AV et al (2005) Release of ATP in the ventral medulla

during hypoxia in rats: role in hypoxic ventilatory response. J

Neurosci (in press).

Contact details:

Professor Nicholas Dale, Department of Biological Sciences,

University of Warwick, Coventry, CV4 7AL

n.e.dale@warwick.ac.uk

Further information:

Open only to UK graduates with at least a 2i degree.

http://www2.warwick.ac.uk/fac/sci/bio/research/

http://www.sarissa-biomedical.com

Closing date: 31st March, 2005

The McGill Group for Suicide Studies & The Douglas Hospital Research Centre

NEUROANATOMIST

The McGill Group for Suicide Studies and The Douglas Hospital Research Centre are seeking an independent investigator at the Assistant

Professor level with expertise in basic neuroanatomical cutting-edge techniques as well as human molecular neuropathology to develop an

independent research program and to be actively involved in a research program on the neurobiology of suicide. The successful candidate

should have a strong record of research accomplishments and could be eligible for a Canada Research Chair. This individual will develop

his independent research program in neuroanatomy and manage the Quebec Suicide Brain Bank. He/she will be part of a multidisciplinary

program investigating suicide and topics related to mental health that includes basic, clinical and social scientists. The Douglas Hospital

Research Centre is one of the leading Canadian facilities in mental-health research comprising over 60 independent investigators and

offering exceptional conditions to carry out cutting-edge research in basic and clinical neuroscience.

Applicants should forward their CV and the names and addresses of three references by March 31st 2005 to:

Dr Gustavo Turecki, MD, PhD

McGill Group for Suicide Studies, Douglas Hospital Research Center, 6875, Lasalle Blvd, Montreal, PQ H4H 1R3 Canada

http://www.douglas.qc.ca

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VACANCIES VACANCIES

JOBSJOBSJOBSJOBSJOBS

University of Sheffield

PhD studentship in

electrophysiology and

computational neuroscience

A 3-4 year EPSRC-supported studentship (starting October 2005

or possibly earlier) is available to study signal integration in the

basal ganglia using a combination of in vitro electrophysiology

and computational modelling.

The proposed project is made possible via a recently established

collaboration between the adaptive behaviour research group

(ABRG) in Psychology http://www.shef.ac.uk/~abrg/, and the

laboratory of Dr Kei Cho in Biomedical Sciences

http://www.shef.ac.uk/bms/academic/kc.html. The project

represents a rare opportunity for a student to engage in an

interdisciplinary piece of research in which they will gather and

model their own data. The home Departments have been rated

5A and 5* in the last RAE.

The studentship is open to UK applicants who have a first class

or upper second class degree in either a life science or numerate

discipline. Necessary training will be provided in all aspect of the

work involved, but the relative weighting of physiology and

modelling is flexible.

For informal enquiries contact:

Dr Paul Overton, Department of Psychology,

University of Sheffield, Western Bank, Sheffield, UK.

Tel: 0114 222 6624 Email: p.g.overton@shef.ac.uk

CLOSING DATE: 1st MAY 2005

Organon Research Scotland

Experienced in-vivo

Electrophysiologist

Organon is a major business unit of the Akzo Nobel Pharma

group, which develops produces and sells ethical human

medicines across the world. At our modern drug discovery facility,

situated midway between Edinburgh and Glasgow, we carry out

innovative research in the fields of Psychiatry, Cardiovascular

disease and Analgesia.

This is an excellent opportunity to work as a technical expert in

the design and performance of a range of electrophysiological

experiments.

Reporting to the Team Leader, you will actively contribute to

project work and you will be proactive and innovative in exploiting

new technologies and opportunities within electrophysiology. A

team player with an enthusiasm for coaching others, you will bring

intellectual stimulus and challenge within and across disciplines.

A PhD with proven in-vivo electrophysiology skills (or a graduate

with extensive experience in in-vivo E-phys), you will also have

good understanding of synaptic physiology and sound knowledge

of ion channels. Proactive and results-orientated, yet with a

commitment to team success, you will thrive in a group

environment and you will have the communication skills to match.

In return,we offer an attractive salary and benefits package

(including tailored relocation support where applicable) together

with excellent training and career development opportunities.

To apply, please send your CV and covering letter to

researchjobs@organon.co.uk or alternatively, send to Human

Resources Department, Organon Research Scotland,

Newhouse, Lanarkshire, Scotland, ML1 5SH. Further information

about Organon can be found at www.organon.co.uk

CLOSING DATE FOR APPLICATIONS 17th MARCH 2005

Department of Anatomy

University of Bristol

PhD Studentship (3 years)

Applications are sought for a three-year MRC-funded PhD

studentship supervised by Prof. Elek Molnar, Prof. Zafar Bashir

and Dr. Clea Warburton in the Department of Anatomy's MRC

Centre for Synaptic Plasticity (www.bris.ac.uk/synaptic, rated

Grade 6* in the 2001 RAE). This project will investigate the

molecular and cellular bases of cognitive impairments in type II

diabetes and the underlying roles of synaptic plasticity and

changes in glutamate receptors by utilizing integrated molecular,

biochemical, immunocytochemical, pharmacological, electrophysiological

and behavioural approaches. Informal enquiries

may be made by e-mail Elek.Molnar@bristol.ac.uk.

Applicants must have (or expect to receive) a first or upper

second class degree in neuroscience, biochemistry,

pharmacology, physiology or other appropriate discipline. This

three-year studentship includes a scholarship of around £12,000

per year and covers University fees of around £3,085 per year.

Applicants must hold UK citizenship to be eligible for the

studentship. The successful student will be registered for a PhD

(MSc in the first instance) and will be affiliated with the

multidisciplinary MRC Centre for Synaptic Plasticity.

Formal applications with a detailed CV, statement of

research interests and the names and addresses of two

academic referees should be sent to Prof. Elek Molnar, MRC

Centre for Synaptic Plasticity, Department of Anatomy,

University of Bristol, School of Medical Sciences, University

Walk, Bristol BS8 1TD, E-mail: Elek.Molnar@bristol.ac.uk.

Applications are invited as soon as possible

CLOSING DATE 31st MARCH 2005

Division of Clinical Neuroscience

University of Glasgow

PhD Studentship in Ligand

Development for Molecular

Brain Imaging

Applications are invited for a PhD studentship funded by a BBSRC-

GlaxoSmithKline Partnership CASE award to develop a novel brain

imaging tracer for the noradrenaline transporter. The aim is to produce

a tracer for imaging the brain by means of Single Photon Emission

Tomography (SPECT) with depression being the primary clinical target.

Techniques will include ligand binding, autoradiography, radiochemistry

and micro-SPECT. The successful candidate will join the

Neuroimaging Group in the Faculty of Medicine including basic

scientists and clinicians from neuroscience, chemistry, brain imaging

physics and psychiatry.

The project will be supervised by Dr Debbie Dewar at the University of

Glasgow and Dr Tom Bonasera at GSK. There will be opportunities for

the student to spend time at GSK during the project. The student will

receive training in a range of techniques suitable for a future career in

brain imaging either in industry or academia.

The position will be available from October 1st 2005 for 3 years.

Informal enquiries may be made by e-mail to Dr Debbie Dewar

(d.dewar@udcf.gla.ac.uk).

Applicants must have (or expect to receive) an upper second class

degree or better in pharmacology, neuroscience, physiology or other

appropriate discipline and must hold UK citizenship to be eligible for

the studentship. An enhancement to the normal BBSRC student

stipend of £3,000 per annum will be made by GSK. Fees and a

contribution to conference attendance are also included.

Applicants should send a full CV with the names and addresses

of two academic referees to Dr Debbie Dewar by email or mail.

Wellcome Surgical Institute, Division of Clinical Neuroscience,

University of Glasgow, Garscube Estate, Glasgow G61 1QH.

CLOSING DATE FOR APPLICATIONS 31st MARCH 2005

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