人體結(jié)構(gòu)與功能 6-Elements of cellular and molecular neuroscience-synapse學(xué)習(xí)資料

SynapseandNeurotransmitter蘇擘神經(jīng)生物學(xué)研究所（6號(hào)樓6620）bxs103@0531-883823292Synapseand

SynapticTransmissionCellBody(Soma):

LifeSupportProteinSynthesisSingleNucleusAxon:LongestprocesstransmitsmessagesawayfromcellbodyDendrites:Multipleprocessesoffcellbody–receivemessagesNeuronsStructure&FunctionIntroductionNeurons67AxonsDendritesTakeinformationawayfromthecellbodyTakeinformationtothecellbodySmoothsurfaceRoughsurface(dendriticspines)Generallyonly1axonpercellUsuallymanydendritespercellNoribosomeHaveribosomesCanhavemyelinNomyelininsulationBranchfurtherfromthecellbodyBranchnearthecellbodyDifferencesbetweenAxonsandDendritesEXCITABLEMembrane:Abletoregulatethemovementofions(charges)acrossandalongmembrane---SIGNALTRANSDUCTIONImportantFeaturesofNeuronsActionPotential13OutlineTypesofsynapsesSignaltransmissionatchemicalsynapsesPrinciplesofsynapticintegration14Synapse:aspecializedjunctionthattransfersnerveimpulseinformationbetweenneuronsorneuronandeffectorcells.15ElectricalsynapsesOccuratspecializedsitescalledgapjunctionCommoninnon-neuralcells(astrocytes)andearlyembryonicstagesChemicalsynapsesPredominatesinthematurehumannervoussystem

TypesofSynapses16AxosomaticsynanpseAxodendriticsynapseAxoaxonicsynapseGray’s

TypeIGray’sTypeII1718Electrical

SynapseGapjunctionAdjacentcellselectricallycoupledthroughachannel.IoniccurrentCytoplasmcontinuousNosynapticcleft-3.5nmBriefdelay

Bidirectional19RapidTransmissionofSignalatElectricalSynapsesAnactionpotentialinthe

presynaptic

neuroncausesthepostsynapticneuron

tobedepolarizedwithinafractionofa

millisecond.20GapjunctionsChannels:ConnexonDiameteris2nm6subunits:connexin21

Thechemicalsynapseisaspecializedjunctionthattransfersnerveimpulseinformationfromapresynapticmembranetoapostsynapticmembraneusingneurotransmitters.AxodendriticsynapseAxosomaticsynanpseAxoaxonicsynapse22ChemicalSynapsesPresynapticelementSynapticvesiclesActivezoneSynapticcleftPostsynapticdensity23Neurotranmitters20-50nmcleftSyanpticdelay:1-5msorlongerunidirectionalChemicalSynapses24Chemicalsynapses

asseenwithelectronmicroscope25電鏡冰凍蝕刻技術(shù)顯示突觸結(jié)構(gòu)26ElectricalSynapseChemicalSynapseDistancebetweenpre-andpostsynapticcellmembranes3.5nm20-50nmCytoplasmiccontinuitybetweenpre-andpostsynapticcellsYesNoUltrastructuralcomponentsGap-iunctionchannelsPresynapticvesiclesandactivezones;postsynapticreceptorsAgentoftransmissionIoncurrentChemicaltransmitterSynapticdelayVirtuallyabsentSignificant:atleast0.3ms,usually1-5msorlongerDirectionoftransmissionUsuallybidirectionalunidirectionalDistinguishingPropertiesofElectricalandChemicalSynapses27OutlineTypesofsynapsesSignaltransmissionatchemicalsynapsesPrinciplesofsynapticintegration28Signaltransmissionatchemicalsynapses

Fromapresynapticmembranetoapostsynapticmembraneusingneurotransmitters29SignalTransmissionatChemicalSynapsesNeurotransmittersNTReceptorsEPSPandIPSP30NeurotransmittersPrecursortransportSynthesisStorageReleaseActivationTerminationdiffusion,degradation,uptake,autoreceptors

31PresynapticAxonTerminalPostsynapticMembraneTerminalButtonDendriticSpine32(1)PrecursorTransport33___NT(2)Synthesisenzymes/cofactors34(3)Storageinvesicles35SynapseVesiclesNTTerminalButtonDendriticSpine36SynapseTerminalButtonDendriticSpine(4)ReleaseReceptors37SynapseTerminalButtonDendriticSpineAP38Ca2+Exocytosis39ReleaseQuantareleaseEachvesiclecontainsonequantaofneurotransmitter(approximately7000molecules)

40(5)Activation41(6)Termination42(6.1)Terminationby...

Diffusion43(6.2)Terminationby...Enzymaticdegradation44(6.3)Terminationby...

Reuptake45(6.4)Terminationby...

AutoreceptorsA46SynthesisandStorageA:peptideB:amineandaminoacid47AmodelforCa2+-triggeredvesiclefusion48Ca2+CAMCAMKII49AelectronmicroscopyviewofNTrelease50Finestructureofvesiclefusionsites

51NTReceptorsTransmitter-gatedionchannelsG-protein-coupledreceptorsAutoreceptor52Transmitter-gatedionchannels53G-protein-coupledreceptors(GPCR)54AutoreceptorInthemembraneofthepresynapticterminalG-protein-coupledreceptorsRegulatesNTreleaseandsynthesisA55①Neurotransmitterreleaseatallpresynapticterminalsonacellresultsinreceptorbinding,whichcausestheopeningorclosingofspecificionchannels.②Theresultingconductancechangecausescurrenttoflow,whichmaychangethemembranepotential.③Thepostsynapticcellsums(orintegrates)alloftheEPSPsandIPSPs,resultinginmoment-to-momentcontrolofactionpotentialgeneration.Eventsfromneurotransmitterreleasetopostsynapticexcitationorinhibition56Excitatorypostsynapticpotential

(EPSP)AnAParrivinginthepresynapticterminalcausethereleaseofneurotransmitterThemoleculesbindandactivereceptoronthepostsynapticmembrane57Openingtransmitter-gatedionschannels(Na+)inpostsynaptic-membraneBothanelectricalandaconcentrationgradientdrivingNa+intothecell;Thepostsynapticmembranewillbecomedepolarized(EPSP).Excitatorypostsynapticpotential(EPSP)58Inhibitorypostsynapticpotential(IPSP)Aimpulsearrivinginthepresynapticterminalcausesthereleaseofneurotransmitter;ThemolecularbindandactivereceptorsonthepostsynapticmembraneopenCI-or,sometimesK+channels;MoreCI-enters,K+outerthecell,producingahyperpolarizationinthepostsynapticmembrane.59Excitatory Inhibitory Depolarization HyperpolarizationNa+influx K+efflux

orCl-influxmorelikelytofire lesslikelyEPSP IPSPEPSPs&IPSPs’differentiations60TwocategoriesofCNSsynapticmembranedifferentiationsTypeIsynapsestypicallycontactspecializedprojectionsonthedendritesspines,lesscommonlycontacttheshaftsofdendrites.TypeIIsynapsesoftencontactthecellbody.61Gray’s

TypeIExcitatorysynapses:permeabletoNa+andK+(N-AchR)

Gray’stypeI:RoundsynapticvesiclesLargeactivezone(1-2um2)

Widesynapticcleft(30nm)Extensivepostsynapticdenseregions62Gray’sTypeIIInhibitorysynapses:permeabletoCl-

(GABA,Glycine)Gray’stypeII:FlattenedsynapticvesiclesSmallactivezone(<1um2)

Narrowsynapticcleft(20nm)Intensivepostsynapticdenseregions63OutlineTypesofsynapsesSignaltransmissionatchemicalsynapsesPrinciplesofsynapticintegration64MostCNSneuronsreceivethousandsofsyanpticinputsthatactivedifferentcombinationsoftransmitter-gatedionchannelsandGPCRs.Thepostsynapticneuronintegratesallofthesesignalsandgiverisetoasimpleformofoutput:actionpotentials.PrinciplesofSynapticIntegration65SpatialsummationTemporalsummationEPSPSummation66SpatialsummationTheaddingtogetherofEPSPsgeneratedsimultaneouslyatmanydifferentsynapsesonadendrite.TwoormorepresynapticinputsareactiveatthesametimeAspace(spatial)dependentprocess.OccursinaConvergentSynapse67TemporalsummationTheaddingtogetherofEPSPsgeneratedatthesamesynapseiftheyoccurinrapidsuccession,within1-15msecofoneanother.ThesamepresynapticfiberfiresAPinquicksuccessionATime(Temporal)dependentprocessOccursinaDivergentSynapse68SummationofpostsynapticpotentialsEPSPs&IPSPssummateCANCELEACHOTHER69-70mv+--EPSPIPSP+70DivergentsynapseandconvergentsynapseSynapticInhibitionSynapticFacilitation71DivergentSynapseAjunctionthatoccursbetweenapresynapticneuronandtwoormorepostsynapticneurons(ratioofpretopostislessthanone).

Thestimulationofthepostsynapticneuronsdependsontemporalsummation.72PresynapticneuronsPostsynapticneuronConvergentSynapseAjunctionbetweentwoormorepresynapticneuronswithapostsynapticneuron(theratioofpretopostisgreaterthanone).Thestimulationofthepostsynapticneurondependsonthespatialsummation.73SynapticInhibitionPresynapticinhibitionPostsynapticneuronproducedecreasedEPSPPostsynapticinhibitionPostsynapticneuronproduceIPSP74PresynapticinhibitionTheinhibitionoccursatthepresynapticterminalsbeforethesignaleverreachesthesynapseCandAformanaxon-axonsynapse(presynapticsynapse).NeuronChasnodirecteffectonneuronB,butitexertapresynapticeffecttodecreasetheamountofneurotransmitterreleasedfromA.CAB75ExcitatorySynapseAactiveBmorelikelytofireAdda3rdneuron~AB+PresynapticInhibition76ExcitatorySynapseAxon-axonsynapseCisinhibitory~AB+PresynapticInhibitionC-77ExcitatorySynapseAB+PresynapticInhibitionC-CactivelessNTfromAwhenactiveBlesslikelytofire~78PostsynapticinhibitionEffectofinhibitorysynapsesonthepostsynapticmembraneInhibitoryinterneuronreleaseinhibitorytransmittersandthepostsynapticneuronproduceIPSPAfferentcollateralinhibition(reciprocalinhibition)Recurrentinhibition79ReciprocalinhibitionAfferentfibersexcitesthemotorneuronstoextensormuscle.Anditsbranchesexciteaninterneuron,whichsecretetheinhibitorytransmitteratsynapsesonthemotorneuronstoflexormuscle(IPSP)80RecurrentinhibitionNeuronsmayalsoinhibitthemselvesinanegativefeedbackfashion.Eachspinalmotorneuronregularlygivesoffarecurrentcollateralthatsynapseswithaninhibitoryinterneuron(Renshawcell