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1、2+CaSignalinginDendriticSpines12BernardoL.SabatiniandKarelSvoboda1DepartmentofNeurobiology,HarvardMedicalSchool,220LongwoodAvenue,Boston,MA02115,USA,bsabatini@hms.harvard.edu2JaneliaFarmResearchCampus,HHMI,19700HelixDrive,Ashburn,VA20147,USA,svobodak@janelia.hh
2、mi.orgAbstract.Dendriticspinesareneuronalmicrocompartmentsthatarediffusionallyisolated2+fromtheirparentdendritesandneighboringspines.OpticalstudiesofspineCadynamics2+2+haverevealedtheCasourcesandCaclearancemechanismsunderavarietyofexperimentalconditionsandindiv
3、erseexperimentalsystems.Herewereviewour2+understandingofCasignalinginspines,pointoutgapsinourknowledge,anddiscussthelimitsoftheexistingexperimentaltechniques.1Introduction2+Postsynapticcalcium(Ca)signalscouplesynaptictransmissionandneuronalexcitationtocomplexin
4、tracellularbiochemicalsignalsandtransductionpathways.2+OfparticularinterestareCaaccumulationsindendritesanddendriticspines.Spine2+Caaccumulationstriggerlong-term-potentiation(LTP)anddepression(LTD)ofsynaptictransmission(75).Theyalsotriggerstructuralplasticityof
5、dendriticspines(123),activatetranscriptionalprograms(30),andinducecytotoxicity(114).Howdoesonesecondmessengerparticipateinthesedisparatefunctions?2+ThediversefunctionsofCacanlikelybeattributedinparttothediverse2+molecularpathwaysunderlyingCainflux.Dependingonth
6、estimulusconditions,2+2+Cacanenterthespinecytoplasmthroughvoltage-sensitiveCachannels2+(VSCCs),synapticglutamatereceptors,Ca-inducedCareleaseandotherpathways.2+Inaddition,Casignalswithdifferentamplitudesanddurationslikelyhavedifferent2+meaningsforpostsynapticsi
7、gnaltransduction.ThedynamicsofspineCasignals2+dependonthepropertiesoftheCasources,ontheconcentrationandaffinityof2+2+endogenousCabuffers,theefficiencyofCaextrusion,andthelocalmorphologyofthespineandsurroundingdendrite.Theadventoftwo-photonexcitationlaserscannin
8、gmicroscopy(TPLSM)(16)hasallowedhigh-resolutionimaginginintactbrainslicesandevenintheintact2+brain.TPLSMtogetherwithCaimagingandtwo-photonphotorelease(TPPR)ofJ.W.Hell,M.D.Eh
