光遗传技术比较好的一篇nature综述_精品文档.pdf
- 文档编号:3210227
- 上传时间:2022-11-20
- 格式:PDF
- 页数:12
- 大小:2.03MB
光遗传技术比较好的一篇nature综述_精品文档.pdf
《光遗传技术比较好的一篇nature综述_精品文档.pdf》由会员分享,可在线阅读,更多相关《光遗传技术比较好的一篇nature综述_精品文档.pdf(12页珍藏版)》请在冰豆网上搜索。
298VOLUME15|NUMBER2|FEBRUARY2012natureneurOSCIenCeartICleSRetinalganglioncell(RGC)projectionstothebrainformstereo-typicmapsforeyeoforiginandretinotopiclocation,makingthemanidealmodelsystemtostudythedevelopmentandplasticityofpreciselypatternedneuralcircuits1,2.Theinitialformationofthesevisualcircuitsisthoughttobeguidedbymolecularcues3,whereastherefinementandmaintenance46oftheseconnectionsseemstobeactivitydependent7.Substantialevidencesupportsageneralroleforactivity-dependentbinocularcompetitioninretinofugalmapdevel-opment.Forinstance,arelativeincreaseinactivityinoneeyeleadstotheexpansionofthateyestargetterritoryinthedorsallateralgenicu-latenucleus(dLGN)8,9,indicatingthatthemoreactiveeyemakesandfurtherstrengthensmoretargetsynapseswhenitisatacompeti-tiveadvantage.Hebbiansynapticlearningrulesthatmaymediatetheactivity-dependentdevelopmentofvisualmapshavebeenobservedinavarietyofretinofugalsystems,includingspike-timingdependentplasticityatretinotectalsynapsesintadpolesinvivo10andbursttimingdependentplasticityatretinogeniculate11andretinocollicular12synapsesinrodentsinvitro.Theseobservationssuggestthatsynapticconnectionsarefunctionallystrengthenedwhencellsaresynchronouslyactiveandweakenedwhencellsareasynchronouslyactiveovertimewindowsthataredistinctindifferentmodelsystems13.Ithaslongbeenpostulatedthatthetimingofspontaneouswave-likeactivityinRGCs14iscriticalfortheestablishmentandmaintenanceofeye-specificsegregationthroughaHebb-basedsynapticlearningrule11,13beforetheonsetofvision.Theshortdurationofretinalwavesrelativetotheintervalbetweenwavesisthoughttoasynchronouslyactivatethetwoeyes,resultingintherefinementofeye-specificdomains15.Evidenceforthistimingmodelforbinocularcompetitionislimited,withtheonlydirectexperimentalsupportcomingfromclassiccatexperimentsinwhichartificiallyasynchronousstimulationoftheopticnervesproducedneuronsthatrespondedpredominantlytoonlyoneeye,whereasstimulationoftheoptictract,whichsynchro-nouslyactivatesRGCafferentsfrombotheyes,causedmostcellsinvisualcortextobecomefunctionallybinocular16.Similarly,alternat-ingmonocularocclusionincatsresultsinreducedcorticalbinocular-ityanddisrupteddepthdiscrimination17.However,theseexperimentswererestrictedtoaphysiologicalanalysisofbinocularityinthecortexandmanipulatedRGCactivityaftertheonsetofnormalvisualexperi-ence,wheneyesegregationinthedLGNandvisualcortexhasalreadyemerged2,18.Becauseithasbeendifficulttopreciselymanipulateneo-natalRGCactivityinmammalsinvivo,theroleoftimingintheinitialdevelopmentofvisualmapsremainsunexplored.Wechronicallymanipulatedretinalactivityinmicebeforetheonsetofvisionoverarangeoftimescalesinvivobyexpressingthelight-gatedcationchannelChannelrhodopsin-2(ChR2)19directlyinRGCsusingtransgenicandviraltransfectionmethods20,21.Light-drivenactivationofChR2-expressingRGCstriggeredpreciselytimedpost-synapticcalciumsignalsinthesuperiorcolliculus,demonstratingthatoptogenetictechniquescanreliablydriveneuronalresponseevenearlyinvisualdevelopment.Whenthetwoeyesweresynchronouslystimu-lated,wefoundthattheinitialemergenceofeye-specificdomainswasdisrupted,whereasasynchronousstimulationimprovedsegregation.Aftereye-specificdomainswerealreadyestablishedinthesuperiorcolliculusanddLGN,asynchronousstimulationhadnoeffect,butsyn-chronousstimulationcauseddomainstodesegregate.Thedisruptiveeffectofoptogeneticstimulationoneyesegregationwanedasthetimedifferencebetweenstimulationoftheeyesincreasedbeyond100ms,whichsuggestsasub-secondtimewindowforbinocularcompeti-tion.Ofnote,whensynchronousstimulationdisruptedeye-specific1DepartmentofNeurobiology,YaleUniversity,NewHaven,Connecticut,USA.2DepartmentofOphthalmology&VisualSciences,YaleUniversity,NewHaven,Connecticut,USA.CorrespondenceshouldbeaddressedtoM.C.C.(michael.crairyale.edu).Received8September;accepted9November;publishedonline18December2011;doi:
10.1038/nn.3007VisualmapdevelopmentdependsonthetemporalpatternofbinocularactivityinmiceJiayiZhang1,JamesBAckman1,Hong-PingXu1&MichaelCCrair1,2Binocularcompetitionisthoughttodriveeye-specificsegregationinthedevelopingvisualsystem,potentiallythroughHebbiansynapticlearningrulesthataresensitivetocorrelationsinafferentactivity.Alteringretinalactivitycandisrupteye-specificsegregation,butlittleisknownaboutthetemporalfeaturesofbinocularactivitythatmodulatevisualmapdevelopment.Weusedoptogenetictechniquestodirectlymanipulateretinalactivityinvivoandidentifiedacriticalperiodbefor
- 配套讲稿:
如PPT文件的首页显示word图标,表示该PPT已包含配套word讲稿。双击word图标可打开word文档。
- 特殊限制:
部分文档作品中含有的国旗、国徽等图片,仅作为作品整体效果示例展示,禁止商用。设计者仅对作品中独创性部分享有著作权。
- 关 键 词:
- 遗传 技术 比较 一篇 nature 综述 精品 文档