Synaptic Plasticity (Section 1, Chapter 7) Neuroscience Online

(Homo from the Greek meaning the same.) Extrinsic plasticity, or heterosynaptic plasticity, is a change in the strength of a synapse brought about by activity ... SynapticPlasticity(Section1,Chapter7)NeuroscienceOnline:AnElectronicTextbookfortheNeurosciences|DepartmentofNeurobiologyandAnatomy-TheUniversityofTexasMedicalSchoolatHouston SkiptoMainContentSkiptoNavigation(accesskeyn) Home TableofContents FurtherReading Section1:CellularandMolecularNeurobiology       Chapter7:SynapticPlasticity JohnH.Byrne,Ph.D.,DepartmentofNeurobiologyandAnatomy,McGovernMedicalSchool Videooflecture 7.1SynapticPlasticity Historically,itwasgenerallythoughtthattheroleofthesynapsewastosimplytransferinformationbetweenoneneuronandanotherneuronorbetweenaneuronandamusclecell.Inaddition,itwasthoughtthattheseconnections,onceestablishedduringdevelopment,wererelativelyfixedintheirstrength,muchlikeasolderjointbetweentwoelectroniccomponents.Oneexcitingdevelopmentinneurobiologyoverthepastfortyyearsistherealizationthatmostsynapsesareextremelyplastic;theyareabletochangetheirstrengthasaresultofeithertheirownactivityorthroughactivityinanotherpathway.Manythinkthatthissynapticplasticityiscentraltounderstandingthemechanismsoflearningandmemory. Therearetwogeneralformsofsynapticplasticity,intrinsicandextrinsic.Intrinsicmechanisms,alsoknownashomosynapticmechanisms,refertochangesinthestrengthofasynapsethatarebroughtaboutbyitsownactivity.(HomofromtheGreekmeaningthesame.)Extrinsicplasticity,orheterosynapticplasticity,isachangeinthestrengthofasynapsebroughtaboutbyactivityinanotherpathway. Figure7.1 HomosynapticPlasticity.Therearetwotypesofintrinsicorhomosynapticplasticity,synapticdepressionandsynapticfacilitation.Synapticdepressionandfacilitationarenotalwaysfoundatthesamesynapse.Somesynapsesexhibitonebutnottheother,whereassomesynapsesexhibitboth.Figure7.1Billustrateshomosynapticplasticityatthesynapsebetweena1Aafferentfiberandaspinalmotorneuron.AnactionpotentialinthesensoryneuronproducesanEPSPinthemotorneuron.Asecondactionpotentialinthesensoryneuron,200msecafterthefirst,producesanEPSPthatissmallerthanthatproducedbythefirstactionpotential.Thisphenomenoniscalledsynapticdepression.Theefficacyofsynaptictransmissionisnotconstant;itvariesdependinguponthefrequencyofstimulation.Themechanismsofsynapticdepressionvarybutonecommonmechanismisdepletionoftheavailabletransmitter.Thesecondoftwoactionpotentialswillreleaselesstransmitterbecauselesstransmitterisavailabletobereleased.(SeeFigure7.2A) Figure7.1Cillustratesthesecondformofhomosynapticplasticity,synapticfacilitation.Thisparticularexampleisknownaspaired-pulseortwin-pulsefacilitation.TwoactionpotentialsinthepresynapticcellproducetwoEPSPsinthepostsynapticcell.Thefirstactionpotentialproducesa1mVEPSP,butthesecondactionpotential,whichoccursabout20msecafterthefirst,producesanEPSPthatislargerthantheEPSPproducedbythefirst.Inthisexample,itistwiceaslargeasthefirstone.ThisdoublingoftheEPSPrepresentsthesynapticfacilitation.ThenetEPSPis3mV.ThroughtheprocessoftemporalsummationthesecondEPSP(2mV)addstotheamplitudeofthefirstEPSP(1mV). Figure7.2 Onemechanismcontributingtotwinpulsefacilitationisresidualcalcium.AnactionpotentialleadstotheopeningofCa2+channelsandtheinfluxofCa2+,whichleadstothereleaseoftransmitter.Nowconsiderthefateofthecalciumafterthefirstactionpotential(Figure7.2B).Ca2+levelswilldeclinebacktotheirinitiallevel,butthisrecoverywillnotoccurinstantaneously.Thus,ifasecondactionpotentialisinitiatedatatimeduringwhichthecalciumhasnotyetrecoveredtoitsbasallevel,thecalciuminfluxassociatedwiththesecondspikewilladdtothe"residualcalcium"thatisleftoverfromthefirst.Theneteffectisthatthetotalconcentrationofcalciumwillbegreaterafterthesecondspikethanitwasafterthefirst,andmoretransmitterwillbereleased. Anotherintrinsictypeofsynapticplasticityiscalledpost-tetanicpotentiation(PTP).Itisanextremeexampleoffacilitationdefinedasarelativelypersistent(minutes)enhancementofsynapticstrengthfollowingabrieftrainofspikes(atetanus). Figure7.3 7.2HeterosynapticFormsofSynapticPlasticity Figure7.4 Justastherearetwotypesofhomosynapticplasticity,therearetwotypesofheterosynapticplasticity.Beforediscussingheterosynapticplasticity,itisusefultoreviewthetypesofsynapsesthatarepresentinthecentralnervoussystem.Threebroadcategoriesofsynapsesarefoundinthecentralnervoussystem.(SeealsoChapter8) Axosomaticsynapsesaresynapsesthataremadeontothesomaorcellbodyofaneuron. Axodendriticsynapses,probablythemostprominentkindofsynapses,aresynapsesthatoneneuronmakesontothedendriteofanotherneuron. Axoaxonicsynapsesaresynapsesmadebyoneneuronontothesynapseofanotherneuron.Axoaxonicsynapsesmediatepresynapticinhibitionandpresynapticfacilitation. Figure7.5 Figure7.5illustratesthetwomajortypesofheterosynapticplasticity;presynapticinhibitionandpresynapticfacilitation.Presynapticinhibitionisnotanesotericphenomenon.Itisveryprominentinthespinalcordandregulatesthepropagationofinformationtohigherbraincenters.AnactionpotentialinthepresynapticcellproducesanEPSPinthepostsynapticcell.Themodulatorycell(M1)makesanaxoaxonicsynapsewiththepresynapticcell.AfterfiringcellM1,theEPSPinthepostsynapticcellissmaller.Thisphenomenoniscalledpresynapticinhibition,becausecellM1regulatestheabilityofthepresynapticcelltoreleasetransmitter.Themodulatorytransmitterengagesmetabotropic-typereceptorsthatactivateasecondmessengersystemthatphosphorylatesCa2+channelsinsuchawaythattheCa2+channelsopenlessreadily.FewerCa2+channelsareopenedwithasubsequentactionpotentialinPreandthereforetheCa2+influx(ICa)willbereduced.LessCa2+influxleadstolesstransmitterreleaseandasmallerEPSP. Thephenomenoncomplementarytopresynapticinhibitionispresynapticfacilitation.M1iscapableofincreasingthestrengthofthesynapticpathway.AsaresultoftheactivationofasecondmessengercascadebyM1,anactionpotentialinthepresynapticterminalleadstoagreateramountofCa2+influx,andthereforemoretransmitterisreleased. 7.3Long-TermPotentiation(LTP) Averyenduringformofsynapticplasticityiscalledlong-termpotentiation(LTP).Itcanhavebothhomosynapticandheterosynapticcomponents.Anelectricshock(teststimulus)toafferentfibersproducesanEPSP(Figure7.6).Ifthepathwayisrepeatedlystimulated(e.g.,everyminute),theamplitudeofEPSPisconstant. Atetanusproducespost-tetanicpotentiation(PTP)thatdiesawayafterseveralminutes.WhatisleftisaveryenduringenhancementoftheEPSP.ThereisexcitementaboutLTPbecauseitisthekindofmechanismnecessarytostorememory(Figure7.7).       Figure7.6   Figure7.7 Figure7.8 TheNMDA-typereceptoriscriticalforsomeformsofLTP,inparticularLTPattheCA3-CA1synapseinthehippocampus.ThepostsynapticspinesofCA1neuronshavetwotypesofglutamatereceptors;NMDA-typeglutamatereceptorsandtheAMPA-typeglutamatereceptors(Figure7.8).BothreceptorsarepermeabletoNa+andK+,buttheNMDA-typehastwoadditionalfeatures. First,inadditiontobeingpermeabletoNa+,italsohasasignificantpermeabilitytoCa2+. Second,thischannelisnormallyblockedbyMg2+. Evenifglutamatebindstothechannelandproducesaconformationalchange,thereisnoeffluxofK+orinfluxofNa+orCa2+becauseitis"pluggedup"bytheMg2+(Figure7.8A).Thus,aweakteststimuluswillnotopenthischannelbecauseitisblockedbyMg2.AweakteststimuluswillproduceanEPSP,butthatEPSPwillbemediatedbytheAMPAreceptor. Nowconsidertheconsequencesofatetanus(Figure7.8B).Becauseofthetetanus,therewillbespatialandtemporalsummationoftheEPSPsproducedbythemultipleafferentsynapsesonthecommonpostsynapticcell(Figure7.6).Consequently,themembranepotentialofthepostsynapticneuronwillbecomeverydepolarized.Becausetheinsideofthecellbecomespositive,thepositivelychargedMg2+is"thrust"outofthechannel(Figure7.8B).Ca2+thenentersthespinethroughtheNMDAreceptor.ThatCa2+activatesvariousproteinkinases,whichthentriggerlong-termchangesinsynapticstrength. Oneofthelong-termchangesinvolvestheinsertionofadditionalAMPAreceptors(Figure7.8C). Consequently,theglutamatereleasedbyateststimulusafteraLTP-inducingtetanuswillopenagreaternumberofchannelsandtherebyproducealarger(potentiated)EPSP(Figure7.8C). InadditiontoanincreaseinthenumberofpostsynapticAMPAreceptors,thereisevidencethatagreateramountoftransmitterisreleasedfromthepresynapticneurons. Thecombinationofthepresynapticandpostsynapticeffectswouldactsynergisticallytoincreasethesizeofthesynapticpotentialinthepostsynapticneuron. 7.4Summary Figure7.9 Agivenpostsynapticneuronreceivessynapticinputfromanumberofdifferentsources.Therearethetraditionaltypeofaxosomaticandaxodendriticsynapses.Thesecanbeeitherexcitatoryorinhibitory.Inaddition,thesynapticresponsescanbemediatedbybothionotropicandmetabotropicreceptors.Thepresynapticcellscanbemodulatedthroughpresynapticinhibitionandpresynapticfacilitation.Considerthatanyonepostsynapticcellmakesandreceives10,000connectionswithothercellsandthatthismodulecanberecapitulatedineachofthebillionsofcellsinthenervoussystem.Itisthisenormouspatternofsynapticconnectionsandtheplasticitythatoccursateachoneofthesesynapseswhichmakesthenervoussystemsoextraordinary. Itisverydifficulttooverestimatetheimportanceofsynaptictransmission.Itiscriticaltothebasicfunctioningofthenervoussystemandappearstobecriticalinlearningandmemory.Also,changesinsynaptictransmissionseemtobecentraltounderstandinganumberofneurologicaldisorderssuchasmyastheniagravisandParkinson'sdisease.Synaptictransmissioniscentraltounderstandingmentaldiseasessuchasschizophrenia,anxiety,anddepression.Amajorthemeofneuroscienceistoidentifythespecifictransmittersystemsinvolvedinthesebraindiseasesanddesignappropriateinterventions.Finally,mostofthepsychoactivedrugsfunctionbyaffectingsomeaspectsofsynaptictransmission.     DonationstoNeuroscienceOnlinewillhelpfunddevelopmentofnewfeaturesandcontent. Contents©1997-Present-McGovernMedicalSchoolatUTHealth DepartmentofNeurobiologyandAnatomy-Sitewebmaster:[email protected] InstructionaldesignandillustrationscreatedthroughtheAcademicTechnology