SystemoftheOrganTheNervousSystem2LIUChuanYong劉傳勇DepartmentofPhysiologyMedicalSchoolofSDUTel88381175(lab)88382098(office)Email:liucy@Website:CharacteristicsoftheCourseIntegration（整合）FrombasictoclinicalCombinewithPBL,LaboratoryandClinicalClerkshipInBilingual(inEnglishandChinese)Chapter2ElementsofCellularandMolecularNeuroscienceReferenceNeuronesandGlialCellsReviewSectionsINeuroneExcitabilityNeuronExcitabilityPart1FacilitatedDiffusionthroughChannelPart2RestingMembranePotentialPart3ActionPotentialsPart4NerveConductionPart5SynapticTransmissionPartIFacilitatedDiffusionthroughChannel

VoltagegatedchannelChemicallygatedchannelMechanicallygatedchannelCategoriesofTransportAcrossthePlasmaMembraneCellmembraneisselectivelypermeabletosomemoleculesandions.Mechanismstotransportmoleculesandionsthroughthecellmembrane:Non-carriermediatedtransport.SimpleDiffusion

（單純擴散）:O2,CO2,steroids,H2OFacilitatedDiffusion

（易化擴散）:ViaCarrier:glucose,aminoacidChannelVoltage,ChemicalandMechanicalgatingchannelActiveTransport

主動轉運PrimaryactivetransportSecondaryactivetransportFacilitateddiffusionthroughchannelsDefinitiontransportproteinscomplexhavewateryspacesallthewaythroughthemoleculeallowfreemovementofcertainionsormolecules.channelproteins.Channelmediateddiffusion.BasicStructureofVoltage-GatedCalciumChannelsCain&Snutch,2010ThealphasubunitisresponsibleforbasicelectrophysiologicalandpharmacologicalpropertiesTheauxiliarysubunitshaveregulatoryrolesPrincipalonealphasubunitandseveralauxiliarysubunitsCharacteristicsofthechannels:selectivelypermeabletospecificsubstances(irons)openedorclosedbygatesFacilitateddiffusionthroughchannelsClassificationofthechannels(accordingtothegatingmechanism):VoltagegatedchannelChemicallygatedchannelMechanicallygatedchannelVoltage-gatedChannelThemolecularconformationofthegaterespondstotheelectricalpotentialacrossthecellmembraneVoltage-gated(ordependent)channel.Voltage-gatedNa+ChannelsManyflavorsnerves,glia,heart,skeletalmusclePrimaryrole:actionpotentialinitiationMulti-subunitchannels(~300kDa)SkeletalNa+Channel:a1(260kDa)andb1(36kDa)NerveNa+Channel:a1,b1,b2(33kDa)gating/permeationmachineryina1subunitsThreetypesofconformationalstates(close,openoractivation,inactivation)-eachcontrolledbymembranevoltageCO2HOutsideNH2++++++++++++InsideNa+Channela1-SubunitStructureIIIIIIIVRVIRLARIGRILRLIKGAKGIR++++++++IFMIFM-Inactivation“Gate”IVS4VoltageSensorNH2CO2Hb1I異亮氨酸；F苯丙氨酸；M甲硫氨酸Mechanismofvoltage-gatedionchannelsworkmovementofthevoltagesensorgeneratesagatingcurrentS4transmembranesegmentmaybevoltagesensorporeformedbyanonhelicalregionbetweenhelix5and6(postulatedtoformbsheets)inactivationgateisinthecytoplasmMolecularstructureAlargeαsubunitsof260kDaandsmallerβsubunitsof30–40kDa

Tetrodotoxin(TTX，河豚毒)selectivelyblockthevoltage-gatedNa+channelNa+ChannelConformationsConductingconformationNon-conductingconformation(s)(atnegativepotentials)(shortlyaftermoredepolarizedpotentials)AnotherNon-conductingconformation(awhileaftermoredepolarizedpotentials)IFMIFMIFMClosedOpenInactivatedOutsideInsideChemically-GatedIonChannelSomeproteinchannelgatesareopenedbythebindingofanothermoleculewiththeproteincausesaconformationalchangeintheproteinmoleculethatopensorclosesthegate.chemicalgating.chemically-gated(ordependent)channelLigand

配體-OperatedACh（乙酰膽堿）ChannelsIonchannelrunsthroughreceptor.Receptorhas5polypeptidesubunitsthatencloseionchannel.2subunitscontainAChbindingsites.Ligand-OperatedAChChannelsChannelopenswhenbothsitesbindtoACh.PermitsdiffusionofNa+intoandK+outofpostsynapticcell.InwardflowofNa+dominates.ProducesEPSPs.Ligand-OperatedAChChannelsMechanically-gatedchannelSomeproteinchannelgatesmaybeopenedbythemechanicaldeformationofthecellmembrane.mechanically-gatedchannel.ItplaysaveryimportantroleinthegenesisofexcitationofthehaircellsOrganofCortiWhensoundwavesmovethebasilarmembraneitmovesthehaircellsthatareconnectedtoit,butthetipsofthehaircellsareconnectedtothetectorialmembranethehaircellgetbent.Therearelittlemechanicalgatesoneachhaircellthatopenwhentheyarebent.K+goesintothecellandDepolarizesthehaircell.(concentrationofK+intheendolymphisveryhigh)WaterChannelThestructureofaquaporin(AQP)Part2MembraneRestingPotentialAconstantpotentialdifferenceacrosstherestingcellmembraneEnablethecellabilitytofireanactionpotential（動作電位）DeterminethebasicsignalingpropertiesofneuronsMembraneRestingPotentialThemembranepotentialresultsfromaseparationofpositiveandnegativechargesacrossthecellmembrane.MembraneRestingPotentialexcessofpositivechargesoutsideandnegativechargesinsidethemembranemaintainedbecausethelipidbilayeractsasabarriertothediffusionofions

anelectricalpotentialdifferencerangesfromabout60to70mVPotentiometerConceptofRestingPotential(RP)Apotentialdifferenceacrossthecellmembraneatthereststageorwhenthecellisnotstimulated.Property:constantorstablenegativeinsiderelativetotheoutsidedifferentindifferentcells.IonChannelsTwoTypesofIonChannelsGatedNon-GatedRestingMembranePotentialNa+andCl-aremoreconcentratedoutsidethecellK+andorganicanions(organicacidsandproteins)aremoreconcentratedinside.IntracellularvsextracellularionconcentrationsIon Intracellular ExtracellularNa+ 5-15mM 145mMK+ 140mM 5mMMg2+ 0.5mM 1-2mMCa2+ 10-7mM 1-2mMH+ 10-7.2M(pH7.2)10-7.4M(pH7.4)Cl- 5-15mM 110mMRestingMembranePotential

Potassiumions,concentratedinsidethecelltendtomoveoutwarddowntheirconcentrationgradientthroughnongatedpotassiumchannelstherelativeexcessofnegativechargeinsidethemembranetendtopushpotassiumionsoutofthecellPotassiumequilibrium-90mVRestingMembranePotentialButwhataboutsodium?ElectrostaticandChemicalforcesacttogetheronNa+ionstodrivethemintothecellTheNa+channelcloseduringtherestingstateNa+ismoreconcentratedoutsidethaninsideandthereforetendstoflowintothecelldownitsconcentrationgradientNa+isdrivenintothecellbytheelectricalpotentialdifferenceacrossthemembrane.Na+electrochemicalgradientEquilibriumPotentials

平衡電位Theoreticalvoltageproducedacrossthemembraneifonlyonekindofioncoulddiffusethroughthemembrane.IfmembraneonlypermeabletoK+,K+diffusesuntil[K+]isatequilibrium.Forceofelectricalattractionanddiffusionare=opposite.CalculatingequilibriumpotentialNernstEquationAllowstheoreticalmembranepotentialtobecalculatedforparticularion.Membranepotentialthatwouldexactlybalancethediffusiongradientandpreventthenetmovementofaparticularion.Valuedependsontheratioof[ion]onthe2sidesofthemembrane.NernstequationEquilibriumpotential(mV),Eion

=

lnRTzF[C]o[C]iwhere, [C]oand[C]i=extraandintracellular[ion] R=Universalgasconstant(8.3joules.K-1.mol-1) T=Absolutetemperature(°K) F=Faradayconstant(96,500coulombs.mol-1) z=Chargeofion(Na+=+1,Ca2+=+2,Cl-=-1)ForK+,with[K+]o=4mmol.l-1and[K+]i=150mmol.l-1At37°C,EK

=-97mVENa=+60mv[K+]o=4mmol.l-1RestingMembranePotentiallessthanEkbecausesomeNa+canalsoenterthecell.TheslowrateofNa+influxisaccompaniedbyslowrateofK+outflux.Dependsupon2factors:Ratiooftheconcentrationsofeachiononthe2sidesoftheplasmamembrane.Specificpermeabilityofmembranetoeachdifferention.

rangesfrom-65to–85mV.TheSodium-PotassiumPump鈉/鉀泵DissipationofionicgradientsisultimatelypreventedbyNa+-K+pumps

extrudesNa+fromthecellwhiletakinginKRestingPotentialFactorsthataffectrestingpotentialDifferenceofK+ionconcentrationacrossthemembranePermeabilityofthemembranetoNa+andK+.ActionofNa+pumpBasicElectrophysiologicalTermsI:Polarization

激化:astateinwhichmembraneispolarizedatrest,negativeinsideandpositiveoutside.Depolarization

去極化:themembranepotentialbecomeslessnegativethantherestingpotential(closetozero).Hyperpolarization

超級化:themembranepotentialismorenegativethantherestinglevel.BasicElectrophysiologicalTermsI:Reverspolarization反激化:areversalofmembranepotentialpolarity.Theinsideofacellbecomespositiverelativetotheoutside.Repolarization復極:restorationofnormalpolarizationstateofmembrane.themembranepotentialreturnsfromdepolarizedleveltothenormalrestingmembranevalue.Part3ActionPotential動作電位SuccessiveStages:RestingStageDepolarizationstageRepolarizationstageAfter-potentialstage(1)(2)(3)(4)ConceptActionpotentialisarapid,reversible可逆轉,andconductivechangeofthemembranepotentialafterthecellisstimulated.Nervesignalsaretransmittedbyactionpotentials.ActionPotentialSequence

Voltage-gatedNa+ChannelsopenandNa+rushesintothecellActionPotentialSequence

Atabout+30mV,Sodiumchannelsclose,butvoltage-gatedpotassiumchannelsopen,causinganoutflowofpotassium,downitselectrochemicalgradientActionPotentialSequence

equilibriumpotentialofthecellisrestored

ActionPotentialSequence

TheSodium–PotassiumPumpislefttocleanupthemess…IonPermeabilityduringtheAPFigure8-12:RefractoryperiodsBasicElectrophysiologicalTermsII(1)Excitability興奮性:TheabilityofthecelltogeneratetheactionpotentialExcitablecells可興奮細胞:Cellsthatgenerateactionpotentialduringexcitation.inexcitablecells(muscle,nerve,secretarycells),theactionpotentialisthemarkerofexcitation.Somescholarsevensuggestthatinexcitablecells,actionpotentialisidenticaltotheexcitation.BasicElectrophysiologicalTermsII(2)Stimulus刺激:asuddenchangeofthe(internalorexternal)environmentalconditionofthecell.includesphysicalandchemicalstimulus.Theelectricalstimulusisoftenusedforthephysiologicalresearch.Threshold閾值(intensity):thelowestorminimalintensityofstimulustoelicitanactionpotential(Threefactorsofthestimulation:intensity,duration,rateofintensitychange)BasicElectrophysiologicalTermsII(3)Typesofstimulus:Thresholdstimulus閾刺激:ThestimuluswiththeintensityequaltothresholdSubthresholdstimulus閾下刺激:ThestimuluswiththeintensityweakerthanthethresholdSuprathresholdstimulus閾上刺激:Thestimuluswiththeintensitygreaterthanthethreshold.ActionPotentialSummaryReductioninmembranepotential(depolarization)to"threshold"levelleadstoopeningofNa+channels,allowingNa+toenterthecellInteriorbecomespositiveTheNa+channelsthencloseautomaticallyfollowedbyaperiodofinactivation.K+channelsopen,K+leavesthecellandtheinterioragainbecomesnegative.Processlastsabout1/1000thofasecond.PropertiesoftheActionPotential“Allornone”phenomenonwithconstantamplitude,timecourseandpropagationvelocityinonecell.PropagationTransmittedinbothdirectioninanervefiberSquidgiantaxonGatedchannelstatesCO2HOutsideNH2++++++++++++InsideNa+Channela1-SubunitStructureIIIIIIIVRVIRLARIGRILRLIKGAKGIR++++++++IFMIFM-Inactivation“Gate”IVS4VoltageSensorNH2CO2Hb1VoltagegatedBut“ready”Not“ready”Activation&FastInactivationSodiumActivationandInactivationVariablevsVoltageActivationGateInactivationgateIfrestingpotentialdepolarizedby15–20mV,thenactivationgateopenedwith5000xincreaseinNa+permeabilityfollowedbyinactivationgateclose1mslaterPositivefeedbackloopNa+enters(depolarization)V-gateNa+channelsopengradedNa+potentialReach“threshold”?IfYES,then...StimulationActionpotentialinitiationS.I.Z.ActionpotentialterminationThresholdPotential閾電位playsakeyroleinthegenesisofactionpotential.acriticalmembranepotentiallevelatwhichanactionpotentialcanoccur.dependentonthegatingpropertyofthevoltage-gatedNa+channels.mostexcitablecell：about15to20mVlessnegativethantherestingpotential.Thethresholdstimulusisjuststrongenoughtodepolarizethemembranetothethresholdpotentiallevel,thereforeitcancauseanactionpotential.ElectrophysiologicalMethodtoRecordMembranePotentialIVoltageClamp電壓鉗

TheNobelPrizeinPhysiologyorMedicine(1963)“fortheirdiscoveriesconcerningtheionicmechanismsinvolvedinexcitationandinhibitionintheperipheralandcentralportionsofthenervecellmembrane”AlanLloydHodgkinAndrewFieldingHuxleyamethodformaintainingVmatanydesiredvoltagelevel(FBA,FeedbackAmplifier)ThevoltageclampTheHodgkin-HuxleyModelofActionPotentialGenerationTriphasicresponseEvidencefora

SodiumCurrentRemoveextracellularsodiumModernproofofnatureofcurrentsUseionselectiveagentsRemovingNa+fromthebathingmedium,INabecomesnegligiblesoIK

canbemeasureddirectly.SubtractingthiscurrentfromthetotalcurrentyieldedINa.ConductanceofNa+andK+channelsVoltage-DependenceofConductanceAnactionpotential

gNaincreasesquickly,buttheninactivationkicksinanditdecreasesagain.

gKincreasesmoreslowly,andonlydecreasesoncethevoltagehasdecreased.TheNa+currentisautocatalytic.AnincreaseinVincreases

gNa,whichincreasestheNa+current,andincreasesV,etc.Hence,thethresholdforactionpotentialinitiationiswheretheinwardNa+currentexactlybalancestheoutwardK+current."fortheirdiscoveriesconcerningthefunctionofsingleionchannelsincells"TheNobelPrizeinPhysiologyorMedicine(1991)ErwinNeherBertSakmannCytoplasmIonchannels"Giga-seal"GlassmicroelectrodeSuction1μmPatchclamp膜片鉗recordingCellMembrane100ms4pAClosedOpenSinglechannelrecordVoltage-dependentChannelConductanceHowchannelconductancesaccumulateNextpageshowsanidealizedversionInactivatingNa+channelcurrentsPart3NerveConductionLocalResponseandSummationNerveConductionLocalResponseDefinition:asmallchangeinmembranepotentialcausedbyasubthresholdstimulusProperties:agradedpotentialPropagation:electronicconductionbesummedbytwowaysSpatialsummationTemporalsummationGraded(local)potentialchanges2xmorechemical=2xmorepotentialchangeExcitatoryExcitatoryInhibitoryTimeMembranePotential(mV)

SpatialSummation

SpatialSummationabcdabcdExcitatoryExcitatoryInhibitoryTimeMembranePotential(mV)

Temporal&

SpatialSummationTemporalSummationabcdabcdDistributionofchannelsLeakchannelseverywhereAxonHillock(TriggerZone)RoleoftheLocalPotentialFacilitatethecell.increaseexcitabilityofthestimulatedcellCausethecelltoexciteonceitissummedtoreachthethresholdpotentialPropagationoftheActionPotentialMyelinatedneuronofthecentralnervoussystemSaltatoryconduction跳躍式傳導:TheactionpotentialjumpsfromnodetonodeSaltatoryConductionSaltatoryConductionThepatternofconductioninthemyelinatednervefiberfromnodetonodeItisofvaluefortworeasons:veryfastconservesenergy.FactorsthataffectthepropagationBioelectricpropertiesofthemembraneVelocityandamplitudeofmembranedepolarization

Part4SynapticTransmissionChemicalsynapse(ClassicalSynapse)Predominatesinthevertebratenervoussystem2.Non-synapticchemicaltransmission3.ElectricalsynapseViaspecializedgapjunctionsDoesoccur,butrareinvertebrateNSAstrocytescancommunicateviagapjunctionsChemicalSynapseTerminalboutonisseparatedfrompostsynapticcellbysynapticcleft.VesiclesfusewithaxonmembraneandNTreleasedbyexocytosis.AmountofNTsreleaseddependsuponfrequencyofAP.

Non-synapticchemicaltransmissionThepostganglionicneuronsinnervatethesmoothmuscles.

Norecognizableendplatesorotherpostsynapticspecializations;

Themultiplebranchesarebeadedwithenlargements(varicosities)thatarenotcoveredbySchwanncellsandcontainsynapticvesicles;Fig.:Endingofpostganglionicautonomicneuronsonsmoothmuscle

Innoradrenergicneurons,thevaricositiesareabout5

m,withupto20,000varicositiesperneuron;

Transmitterisapparentlyreleasedateachvaricosity,atmanylocationsalongeachaxon;

Oneneuroninnervatemanyeffectorcells.Fig.:EndingofpostganglionicautonomicneuronsonsmoothmuscleNon-synapticchemicaltransmissioncontinuedElectricalSynapseImpulsescanberegeneratedwithoutinterruptioninadjacentcells.Gapjunctions:Adjacentcellselectricallycoupledthroughachannel.Eachgapjunctioniscomposedof12connexinproteins.Examples:Smoothandcardiacmuscles,brain,andglialcells.Electriccurrentflow-communicationtakesplacebyflowofelectriccurrentdirectlyfromoneneurontotheotherNosynapticcleftorvesiclescellmembranesindirectcontactCommunicationnotpolarized-electriccurrentcanflowbetweencellsineitherdirectionElectricalSynapsesElectricalSynapseChemicalSynapsePurves,2001TheChemicalSynapseandSignalTransmissionThechemicalsynapseisaspecializedjunctionthattransfersnerveimpulseinformationfromapresynapticmembranetoapostsynapticmembraneusingneurotransmittersandenzymesSynapticconnections~100,000,000,000neuronsinhumanbrainEachneuroncontacts~1000cellsForms~10,000connections/cellHowmanysynapses?Neurotransmitter-communicationviaachemicalintermediarycalledaneurotransmitter,releasedfromoneneuronandinfluencesanotherSynapticcleft-asmallgapbetweenthesending(presynaptic)andthereceiving(postsynaptic)siteChemicalSynapsesSynapticvesicles-smallsphericalorovalorganellescontainchemicaltransmitterusedintransmissionPolarization-communicationoccursinonlyonedirection,fromsendingpresynapticsite,toreceivingpostsynapticsite

ChemicalSynapsesPrecursortransportNTsynthesisStorageReleaseActivationTermination~diffusion,degradation,uptake,autoreceptors1.SynapticTransmissionModelPresynapticAxonTerminalPostsynapticMembraneTerminalButtonDendriticSpine(1)PrecursorTransport___NT(2)Synthesisenzymes/cofactors(3)StorageinvesiclesSynapseVesiclesNTTerminalButtonDendriticSpineSynapseTerminalButtonDendriticSpine(4)ReleaseReceptorsSynapseTerminalButtonDendriticSpineAPCa2+ExocytosisEachvesiclecontainsonequantaofneurotransmitter(approximately5000molecules)–

quantarelease(5)Activation(6)Termination(6.1)Terminationby...Diffusion(6.2)Terminationby...Enzymaticdegradation(6.3)Terminationby...Reuptake(6.4)Terminationby...AutoreceptorsAAutoreceptorsOnpresynapticterminalBindsNT sameaspostsynapticreceptors differentreceptorsubtypeDecreasesNTrelease&synthesisMetabotropicreceptorsSynapticTransmissionAPtravelsdownaxontobouton.VGCa2+channelsopen.Ca2+entersboutondownconcentrationgradient.InwarddiffusiontriggersrapidfusionofsynapticvesiclesandreleaseofNTs.Ca2+activatescalmodulin,whichactivatesproteinkinase.Proteinkinasephosphorylatessynapsins.Synapsinsaidinthefusionofsynapticvesicles.SynapticTransmission(continued)NTsarereleasedanddiffuseacrosssynapticcleft.NT(ligand)bindstospecificreceptorproteinsinpostsynapticcellmembrane.Chemically-regulatedgatedionchannelsopen.EPSP:depolarization.IPSP:hyperpolarization.Neurotransmitterinactivatedtoendtransmission.2EPSPandIPSP(1)Excitatorypostsynapticpotential(EPSP)AnAParrivinginthepresynapticterminalcausethereleaseofneurotransmitter;

Themoleculesbindandactivereceptoronthepostsynapticmembrane;

(1)Excitatorypostsynapticpotential(EPSP)Openingtransmitter-gatedionschannels(Na+)inpostsynaptic-membrane;BothanelectricalandaconcentrationgradientdrivingNa+intothecell;Thepostsynapticmembranewillbecomedepolarized(EPSP).

EPSPNothreshold.Decreasesrestingmembranepotential.Closertothreshold.Gradedinmagnitude.Havenorefractoryperiod.Cansummate.(2)Inhibitorypostsynapticpotential(IPSP)?Aimpulsearrivinginthepresynapticterminalcausesthereleaseofneurotransmitter;?ThemolecularbindandactivereceptorsonthepostsynapticmembraneopenCI-or,sometimesK+channels;?MoreCI-enters,K+outerthecell,producingahyperpolarizationinthepostsynapticmembrane.(IPSPs):Nothreshold.Hyperpolarizepostsynapticmembrane.Increasemembranepotential.Cansummate.Norefractoryperiod.

3SynapticInhibitionPresynapticinhibition:AmountofexcitatoryNTreleasedisdecreasedbyeffectsofsecondneuron,whoseaxonmakessynapseswithfirstneuron’saxon.PostsynapticinhibitionConcept:effectofinhibitorysynapsesonthepostsynapticmembrane.Mechanism:IPSP,inhibitoryinterneuronTypes:

Afferentcollateralinhibition(reciprocalinhibition)

Recurrentinhibition.(1)Postsynapticinhibition

1)ReciprocalinhibitionActivityintheafferentfibersfromthemusclespindles(stretchreceptors)excites(EPSPs)directlythemotorneuronssupplyingthemusclefromwhichtheimpulsescome.

PostsynapticinhibitionAtthesametime,inhibits(ISPSs)thosemotorneuronssupplyingitsantagonisticmuscles.

1)ReciprocalinhibitionThelatterresponseismediatedbybranchesoftheafferentfibersthatendontheinterneurons.

PostsynapticinhibitionTheinterneurons,inturn,secretetheinhibitorytransmitter(IPSP)atsynapsesontheproximaldendritesorcellbodiesofthemotorneuronsthatsupplytheantagonist.Neuronsmayalsoinhibitthemselvesinanegativefeedbackfashion.Eachspinalmotorneuronregularlygivesoffarecurrentcollateralthatsynapseswithaninhibitoryinterneuronwhichterminatesonthecellbodyofthespinalneuronandotherspinalmotorneurons.Theinhibitoryinterneurontosecreteinhibitorymediator,slowsandstopsthedischargeofthemotorneuron.

2)Recurrentinhibition

PostsynapticinhibitionConcept:theinhibitionoccursatthepresynapticterminalsbeforethesignaleverreachesthesynapse.Thebasicstructure:anaxon-axonsynapse(presynapticsynapse),AandB.NeuronAhasnodirecteffectonneuronC,butitexertaPresynapticeffectonabilityofBtoInfluenceC.ThepresynaticeffectMaydecreasetheamountofneuro-transmitterreleasedfromB(Presynapticinhibition)orincreaseit(presynapticfacilitation).

(2)PresynapticinhibitionAABCACBThemechanisms:

?ActivationofthepresynapticreceptorsincreasesCI-conductance,

todecreasethesizeoftheAPreachingtheexcitatoryending,

reducesCa2+entryandconsequentlytheamountofexcitatorytransmitterdecreased.Presynapticinhibition?Voltage-gatedK+channelsarealsoopened,andtheresultingK+effluxalsodecreasestheCa2+influx.ExcitatorySynapseAactiveBmorelikelytofireAdda3dneuron~AB+PresynapticInhibitionExcitatorySynapseAxon-axonsynapseCisinhibitory~AB+PresynapticInhibitionC-ExcitatorySynapseAB+PresynapticInhibitionC-CactivelessNTfromAwhenactiveBlesslikelytofire~4SynapticFacilitation:PresynapticandPostsynapticExcitatorySynapseAactiveBmorelikelytofire~AB+(1)PresynapticFacilitationExcitatorySynapseAB+PresynapticFacilitationC+Cactive(excitatory)moreNTfromAwhenactive(Mechanism:APofAisprolongedandCa2+channelsareopenforalongerperiod.)Bmorelikelytofire~(2)Postsynapticfacilitation:neuronthathasbeenpartiallydepolarizedismorelikelytoundergoAP.-65mv-70mvATRESTVmTimeEPSP+-Depolarization morelikelytofire~Recordhere+5SynapticIntegrationEPSPscansummate,producingAP.Spatialsummation:NumerousPSPconvergeonasinglepostsynapticneuron(distance).Temporalsummation:Successivewavesofneurotransmitterrelease(time).(1)SpatialSummationTheaccumulationofneurotransmitterinthesynapseduethecombinedactivityofseveralpresynapticneuronsenteringtheArea(Space)ofaConvergentSynapse.Aspace(spatial)dependentprocess.-65mv-70mvATRESTvmTime+-SpatialSummation+Multiplesynapses+(2)TemporalSummationTheaccumulationofneurotransmittersinasynapseduetotherapidactivityofapresynapticneuronoveragivenTimeperiod.OccursinaDivergentSynapse.(explainlater)IsaTime(Temporal)dependentprocess.-65mv-70mvATRESTVmTime+-TemporalSummation+Repeatedstimulationsamesynapse~(3)EPSPs&IPSPssummateCANCELEACHOTHERNetstimulationEPSPs+IPSPs=neteffects~-70mv+--EPSPIPSP+6.DivergentandConvergentSynapseDivergentSynapseAjunctionthatoccursbetweenapresynapticneuronandtwoormorepostsynapticneurons(ratioofpretopostislessthanone).Thestimulationofthepostsynapticneuronsdependsontemporalsummation).ConvergentSynapsePresynapticneuronsPostsynapticneuronAjunctionbetweentwoormorepresynapticneuronswithapostsynapticneuron(theratioofpretopostisgreaterthanone).ThestimulationofthepostsynapticneurondependsontheSpatialSummation.Section3NeurotransmittersandReceptors1.BasicConceptsofNTandreceptorNeurotransmitter:Endogenoussignalingmoleculesthatalterthebehaviourofneuronsoreffectorcells.Neuroreceptor:ProteinsonthecellmembraneorinthecytoplasmthatcouldbindwithspecificneurotransmittersandalterthebehaviorofneuronsofeffectorcellsVastar