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Annual Review 2011 - Wellcome Trust

Annual Review 2011 - Wellcome Trust

Untangling the

Untangling the complexityof the brainWhile the broad functions of manyregions of the brain are welldocumented, we do not yetunderstand how individual nervecells – neurons – interact with eachother. Knowing which cells areconnected, and how informationflows through circuits in the brain,will be essential to a full explanationof how our brains work and whatgoes wrong in conditions as diverseas schizophrenia and stroke.With around 100 billion neurons,each one connected to thousandsof others, the brain has an estimated150 trillion connections, or synapses.Mapping these connections is adaunting task but researchpublished in Nature in April 2011described a way to map the functionof individual neurons and theirsynaptic connections inunprecedented detail.Lead author Dr Tom Mrsic-Flogel, aWellcome Trust Research CareerDevelopment Fellow at UniversityCollege London, developed thetechnique and used it to study thevisual cortex – the part of the brainthat processes information from theeye. Within the visual cortex,different nerve cells have differentfunctions. For example, some cellsspecialise in detecting edges inimages; of these, some will beactivated by the detection ofhorizontal edges, others by verticaledges. In this way, the brainconstructs our perceptual imagesof whole objects and scenes.Dr Mrsic-Flogel and colleagues usedhigh-resolution imaging to look intothe visual cortex of the mouse brain,which contains thousands of neuronsand millions of synapses. First, theyidentified those neurons thatresponded to a particular stimulus –detecting a horizontal edge, forexample.Then they applied small electricalcurrents to a subset of these cells tosee which others responded,indicating a synaptic connectionbetween them. Repeating this processmany times, the team was able totrace the function and connectivity ofhundreds of cells.They found that neurons with similarfunctions, such as responding tohorizontal lines, tended to connect toeach other more than to those withother functions. This showed that theneural connections were ordered at alocal level.Using this technique, Dr Mrsic-Flogelis hoping to generate a ‘wiring’diagram of the visual cortex. This willhelp us to understand the fullrepertoire of computations carriedout by the neurons in this brainregion and reveal more about theirconnections with related parts of thebrain that underpin hearing, touchand movement.Applied to the other parts of thebrain, this technique could eventuallyproduce the data needed to develop acomputer model to explain how ourneural networks generate thoughts,sensations and movements.26 | Annual Review 2011

2401 ObjectsA play about Henry Molaison, whoseexperimental surgery for epilepsy in1953 left him unable to form newmemories, won a Fringe First Awardat the 2011 Edinburgh Festival andwas shortlisted for the Carol TamborBest of Edinburgh Award 2011.Part-funded by a Wellcome Trust ArtsAward, 2401 Objects was created bytheatre company Analogue incollaboration with leadingneuroscientists. It was well receivedin the press, earning five stars in theEdinburgh Fringe Review, four stars inthe Telegraph and Times, and ‘Pick ofthe Festival’ in the Sunday Express.Sunburn reveals possible new targetsfor pain reliefIn July 2011, the London PainConsortium, funded by a WellcomeTrust Strategic Award, showed for thefirst time the role of a molecule calledCXCL5 in mediating pain. Theirfindings revealed that CXCL5 wassignificantly overexpressed in the skinof volunteers exposed to UVBradiation. Examination of the biologyof CXCL5 in rats confirmed that itsignificantly reduced the sensitivityto pain caused by UVB radiation. Theteam’s novel approach reverses thetraditional method of studyingdiseases in animal models first, andthen trying to translate the findingsin the clinic.Brain cells protect themselves fromstroke damageScientists at the University of Bristolhave identified how a nerve cell in thebrain protects itself from damageduring stroke. They looked at CA3cells from the hippocampus region ofthe brain, which is involved inmemory and navigation, and foundthat these cells had adenosine A3receptors on their surface.The findings, published in August2011 in the Journal of Neuroscience,showed that CA3 cells’ adenosinereceptors were activated by theadenosine released during a stroke.The activated receptors removedglutamate receptors, making the cellsmore resistant to glutamate, highlevels of which cause brain damage instroke. This natural protectionmechanism in CA3 cells may be usefulin developing strategies to protectother types of nerve cell.From left:Abstract artwork of nerve cells. Laguna Design/SPLA scene from Analogue’s 2401 Objects. Andreas EtterThe CXCL5 molecule reduces sensitivity to the painof sunburn. Shane White/iStockphotoHippocampal neurons with glutamate receptorsshowing. Dr A Irving, University of Dundee/WellcomeImagesHe was a very gracious man, very patient,always willing to try these tasks I wouldgive him. And yet every time I walked inthe room, it was like we’d never met.”Dr Brenda Milner, who carried out many studies ofHenry Molaison’s memoryAnnual Review 2011 | 27

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