Understanding Synapses； Past, Present, and Future理解突触；过去、现在和未来

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1、NeuronPerspectiveUnderstandingSynapses:Past,Present,andFutureThomasC.Su¨dhof1,*andRobertC.Malenka2,*1DepartmentofMolecularandCellularPhysiology2NancyPritzkerLaboratory,DepartmentofPsychiatryandBehavioralSciencesStanfordUniversitySchoolofMedicine,1050ArastraderoRoad,PaloAlto,CA94304USA*Co

2、rrespondence:tcs1@stanford.edu(T.C.S.),malenka@stanford.edu(R.C.M.)DOI10.1016/j.neuron.2008.10.011ClassicalphysiologicalworkbyKatz,Eccles,andothersrevealedthecentralimportanceofsynapsesinbrainfunction,andcharacterizedthemechanismsinvolvedinsynaptictransmission.Buildingonthiswork,majoradv

3、ancesinthepasttwodecadeshaveelucidatedhowsynapsesworkmolecularly.Inthepresentperspec-tive,weprovideashortdescriptionofourpersonalviewoftheseadvances,suggestaseriesofimportantfuturequestionsaboutsynapses,anddiscussideasabouthowbesttoachievefurtherprogressinthefield.Enormousprogresshasbeenm

4、adeinrecentdecadesinouractivezoneproteins,andproteinsofthepostsynapticdensityunderstandingofsynaptictransmissionanditsuse-dependent(e.g.,Choetal.,1992;Broseetal.,1995;Ushkaryovetal.,plasticity.Thedevelopmentofnewtools,inparticularinmolec-1992;Ichtchenkoetal.,1995).Althoughthemolecularcat

5、alogingulargenetics,structuralbiology,electrophysiology,andimagingofsynapticproteinscanbeviewedasmerelydescriptive,thishasledtoadetailedunderstandingofkeyphenomena,suchasworkisaprerequisiteforunderstandingsynapses.Thiseffort2+theCa-triggeringofneurotransmitterreleaseandsomeoftheculminate

6、dinthesystematicanalysisofthesynapticvesicleaskeymechanismsunderlyingsynapticplasticity.Nevertheless,anorganelle(Burre´etal.,2006;Takamorietal.,2006),andthemajortechnicalandintellectualchallengesremain.AsNeurondevelopmentofmodelsforthemolecularorganizationofthepre-turns20,itseemsanapprop

7、riatetimetoprovideabrief,highlysynapticactivezoneandthepostsynapticdensity(Su¨dhof,personalperspectiveonsomeofthemajoradvancesinour2004;KimandSheng,2004;ScannevinandHuganir,2000;understandingofsynapticfunctionoverthelasttwodecades,SchochandGundelfinger,2006).Much,however,r