《精神病學基礎》教學大綱

《精神病學基礎》教學大綱（供精神衛(wèi)生專業(yè)本科使用）濟寧醫(yī)學院精神衛(wèi)生學院（系、部）二00六年六月《精神病學基礎》課程教學大綱課程主任：王克勤開課單位：精神病學基礎教研室課程編碼：0310014課程中文名稱：精神病學基礎課程英文名稱：TheFoundationforPsychiatry《精神病學基礎》課程是精神衛(wèi)生專業(yè)本科高等教育的專業(yè)基礎課程。其基本任務是為更好的預防和治療精神疾病提供有效的理論基礎。精神疾病是特殊復雜的，這主要在于人的精神活動既受生物、心理、社會和自然環(huán)境的多種影響，又反過來能影響到這其中的諸多因素。但人的精神活動的物質基礎是大腦，不管是什么樣的原因，通過什么樣的途徑，最終都要作用于大腦，才能導致精神活動異常。《精神病學基礎》以腦科學為基礎，以與精神病學密切有關的功能神經解剖、神經生化、認知神經科學、神經心理學等領域的相關知識為主要講授內容，是集理論性與應用性為一體的學科。設置本課程的目的是：使學習者全面了解與精神病學密切有關的神經生物學和心理社會科學內容，系統(tǒng)掌握有關的功能神經解剖、神經生化、神經發(fā)育、神經可塑性、認知神經科學、病因學、心理社會科學等方面的基礎知識，具備在臨床工作中全面、客觀的認識、分析、判斷精神疾病的實際技能，從而勝任精神科臨床醫(yī)療和教學工作。學習本課程的要求是：學習者應認識到、生物-心理-社會這種醫(yī)學模式在精神科尤為重要。在學習中，要系統(tǒng)掌握：1、精神活動和行為的神經生物學基礎，2、社會因素和心理活動及行為與大腦的相互作用、相互影響，3、人格和行為模式的形成和可變性。學會在臨床工作中自覺地從生物、心理、社會三個方面全面、深刻地認識、分析、判斷具體的疾病。提高診斷、治療、預防精神疾病的水平，為成為一名高水平的精神科醫(yī)生打下良好的基礎。先修課程要求：神經解剖學、神經生化學、神經病理學、病理生理學、內分泌學和遺傳學。本課程計劃42學時，3.5學分。選用教材：自編英文版《精神病學基礎》教學手段：課堂講授考核方法：閉卷考試教學進程安排表：章節(jié)教學內容學時理論實踐合計1IntroductionofBrainandBehavior22NeuralSignaling23Intraneuronalsignalingpathways24Neurotransmitter45LimbicStructureandBasalGanglia26CerebralCortex47NeuropsychologicalDevelopment28NeuralPlasticity29Memory210EmotionandSocialCognitive211Aetiologyofpsychiatry412ContributionsofthePsychosocialSciencestoHumanBehavior613TheoriesofPersonalityandPsychopathology414PsychologyandPsychiatry:PsychometricandNeuropsychologicalTesting4合計42第一章腦與行為概述一、學習目的通過本章的學習，明確為什么研究腦和行為，理解腦和正常及異常精神活動的關系，掌握神經系統(tǒng)功能原則。本章計劃2學時。二、課程內容1.WhyStudyBrainandBehavior?Thehumanbrainisthebiologicalsubstrateforallofouremotions,cognitiveabilities,andbehaviors—thatis,everythingwefeel,think,anddo.Theaccumulatedresearchsuggeststhreereasonsforlinkingthestudyofbrainandbehavior:⑴Agrowinglistofbehavioraldisorderscanbeexplainedandpossiblycuredbyunderstandingthebrain.Indeed,morethan2000disordersmayinsomewayberelatedtobrainabnormalities.⑵ThebrainisthemostcomplexlivingorganonEarthandisfoundinmanydifferentgroupsofanimals.⑶Howthebrainproducesbothbehaviorandhumanconsciousnessisamajorunansweredscientificquestion.2.MentalhealthandBrainWearedefinedbyourbrainsmorethananyotherorganinourbody.Thebrainoffersendlesspossibilities;whenthebrainmalfunctions,however,anindividualmayfaceanunwelcomedisorder,inmanycases,alive-inguestforlife.Thenumberofpeoplesufferingfrommentalillnessesvaries;whereasschizophreniaaffectsabout1%ofthepopulation,depressionaffectsabout15%,asdoesAlzheimer’sdiseaseinpeopleover65.Althoughexcitingresearchiscurrentlybeingconductedinneurosciencelaboratoriesallovertheworld,acureformentalillnessisstillelusive.3.NeuroscienceinanEvolutionaryContextEvolutionresultsfromthecomplexinterplayofbiologyandenvironment,ofgenesandexperience.Thisongoinginterplayinfluenceshowhumansandotheranimalsbehaveandlearnfromearliestinfancythrougholdage.Experiencecaninfluencethemessagesthatgenesproduce,andgenes,inturn,caninfluenceanorganism’senvironmentandexperience.Predictabledevelopmentalstagesareinitiatedbythegeneticcode,butthedetailsofdevelopmentcanbeinfluencedbychance,byexperience,andbytheenvironment.Thedanceofgeneticandexperientialinfluencescontinuesthroughoutourlivesjustasitdoesinthecontinuingevolutionofourspecies.Experiencescanturnthegenesinneuronson,andthewayinwhichgenesareturnedoninfluencesexperience.Theinfluenceofgenesandexperienceisnotsimplytoformneuronsandplacetheminappropriaterelationswithoneanotherbutalsotoeliminateexcessorfaultyneuronsandconnections,analogouslytothesculptingofastatuefromanunshapedblockofmarble.4.ThePrinciplesofNervousSystemFunctionPrinciple1:Information-ProcessingSequenceintheBrainIs“In→Integrate→Out”Principle2:SensoryandMotorFunctionsthroughouttheNervousSystemAreSeparatedPrinciple3:InputsandOutputstotheBrainAreCrossedPrinciple4:BrainAnatomyandFunctionDisplayBothSymmetryandAsymmetryPrinciple5:TheNervousSystemWorksthroughExcitationandInhibitionPrinciple6:TheNervousSystemFunctionsonMultipleLevelsPrinciple7:BrainComponentsOperateBothParallellyandHierarchicallyPrinciple8:FunctionsintheBrainAreBothLocalizedinSpecificRegionsandDistributedPrinciple9:PatternsofNeuralOrganizationArePlastic三、重點、難點提示和教學手段（一）重點：神經系統(tǒng)的功能原則及行為意義；精神衛(wèi)生和腦的關系。（二）難點：神經系統(tǒng)的功能原則。（三）教學手段：多媒體教學，盡量運用圖片和錄像增加學生的感性認識。雙語教學，講授法（結合提問、臨床病例等進行啟發(fā)式教學等）。（四）教具：多媒體電腦、多媒體投影儀、投影屏幕、多媒體課件、激光筆等四、思考與練習1．精神衛(wèi)生專業(yè)的工作者為什么要研究大腦2．腦的功能原則的行為意義第二章神經信號傳遞一、學習目的通過本章的學習，理解神經細胞信息傳遞的電-化學轉變過程，掌握神經細胞之間信息傳遞的步驟和涉及的結構，了解不同類型的神經細胞膜電位。本章計劃2學時。二、課程內容1.NerveCellsIngeneral,neuronsarecomposedoffourmorphologicallyidentifiedregions:(1)thecellbodyorsoma,whichcontainsthenucleusandcanbeconsideredthemetaboliccenteroftheneuron.(2)Thedendrites,processesthatarisefromthecellbody,branchextensively,andserveasthemajorrecipientzonesofinputfromotherneurons.Onsomeneurons,theshaftsofthedendritesaresmooth.Onothers,theshaftsshownumerousshortspines.(3)theaxon,asingleprocessthatarisesfromaspecializedportionofthecellbody(theaxonhillock)andconveysinformationtootherneurons;and(4)theaxonterminals,finebranchesneartheendoftheaxonthatformcontacts(synapses)generallywiththedendritesorthecellbodiesofotherneurons,releaseneurotransmitters,andtherebyprovideamechanismforinterneuronalcommunication.2.ElectricalPotentialsacrossNerveCellMembranesReceptorpotentialsareduetotheactivationofsensoryneuronsbyexternalstimuli,suchaslight,sound,orheat.Neuronshaveameansofgeneratingaconstantvoltageacrosstheirmembraneswhenatrest.Thisvoltage,calledtherestingmembranepotential.Activationofthesynapsesgeneratessynapticpotentials,whichallowtransmissionofinformationfromoneneurontoanother.Theelectricalsignalsconductedalongaxons(ormusclefibers)bywhichinformationisconveyedfromoneplacetoanotherinthenervoussystemarecalledactionpotentials.3.ChannelsandTransporters3.1.IonChannelsSeveralchannelcategoriesarerecognized.⑴Passive(non-gated)channelsareopenatalltimes,permittingionstomoveacrossthemembrane.⑵Voltage-gatedchannelscontainavoltage-sensitivestringofaminoacidsthatcausethechannelporetoopenorcloseinresponsetochangesinmembranevoltage.⑶Transmitter-gatedchannelsaboundinpostsynapticmembranes.Someareactivateddirectlybytransmittermolecules,othersindirectly.⑷Transductionchannelsareactivatedbyperipheralsensorystimulation.3.2.ActiveTransportersSeveraltypesofactivetransporterhavenowbeenidentified.Althoughthespecificjobsofthesetransportersdiffer,allmusttranslocateionsagainsttheirelectrochemicalgradients.Movingionsuphillrequirestheconsumptionofenergy,andneuronaltransportersfallintotwoclassesbasedontheirenergysources.SometransportersacquireenergydirectlyfromthehydrolysisofATPandarecalledATPasepumps.ThesecondclassofactivetransporterdoesnotuseATPdirectly,butdependsinsteadontheelectrochemicalgradientsofotherionsasanenergysource.3.3.FunctionalPropertiesoftheNa+/K+PumpThischanneliscapableofsimultaneouslyextrudingNa+andimportingK+.Threesodiumionsareexportedforeverytwopotassiumionsimported.Inbothcases,themovementisagainsttheexistingconcentrationgradient.TherequiredenergyforthisactivityisprovidedbytheATPaseenzymethatconvertsATPtoADP.ThegreatertheamountofNa+inthecytosol,thegreateristheactivityoftheenzyme.TheactivityoftheNa+-K+pumpisestimatedtoaccountfor20–40%ofthebrain’senergyconsumption,indicatingitsimportanceforbrainfunction.4.SynapticTransmissionThehumanbraincontainsatleast100billionneurons,eachwiththeabilitytoinfluencemanyothercells.Clearly,sophisticatedandhighlyefficientmechanismsareneededtoenablecommunicationamongthisastronomicalnumberofelements.Suchcommunicationismadepossiblebysynapses,thefunctionalcontactsbetweenneurons.Twodifferenttypesofsynapse—electricalandchemical—canbedistinguishedonthebasisoftheirmechanismoftransmission.4.1.ElectricalSynapsesElectricalsynapsesarescarceinthemammaliannervoussystem.Thestructureofanelectricalsynapseconsistsofthepresynapticandthepostsynapticelement.Themembranesofthetwocommunicatingneuronscomeextremelycloseatthesynapseandareactuallylinkedtogetherbyanintercellularspecializationcalledagapjunction.Gapjunctionscontainpreciselyaligned,pairedchannelsinthemembraneofthepre-andpostsynapticneurons,suchthateachchannelpairformsapore.4.2.ChemicalSynapsesThetypicalchemicalsynapsecomprisesapresynapticmembrane,asynapticcleft,andapostsynapticmembrane.Thepresynapticmembranebelongstotheterminalbouton,thepostsynapticmembranetothetargetneuron.Theboutoncontainssynapticvesiclesloadedwithoneormoreneurotransmitters,togetherwithnumerousmitochondria.Neurotransmitterisreleasedfromtheboutonbyexocytosis,traversesthenarrowsynapticcleft,andactivatesreceptorsinthepostsynapticmembrane.Underlyingthepostsynapticmembraneisasubsynapticweb,inwhichnumerousbiochemicalchangesareinitiatedbyreceptoractivation.4.3.SignalTransmissionatChemicalSynapsesTransmissionatchemicalsynapsesisbasedontheelaboratesequenceofevents.Theprocessisinitiatedwhenanactionpotentialinvadestheterminalofthepresynapticneuron.Thechangeinmembranepotentialcausedbythearrivaloftheactionpotentialleadstotheopeningofvoltage-gatedcalciumchannelsinthepresynapticmembrane.BecauseofthesteepconcentrationgradientofCa2+acrossthepresynapticmembrane(theexternalCa2+concentrationisapproximately10-3M,whereastheinternalCa2+concentrationisapproximately10-7M),theopeningofthesechannelscausesarapidinfluxofCa2+intothepresynapticterminal,withtheresultthattheCa2+concentrationofthecytoplasmintheterminaltransientlyrisestoamuchhighervalue.ElevationofthepresynapticCa2+concentration,inturn,allowssynapticvesiclestofusewiththeplasmamembrane5.Neurotransmitters5.1.CriteriaThatDefineaNeurotransmitterTheneurotransmitteristhesubstancethatisreleasedbysynapticterminalforthepurposeoftransmittinginformationfromonenervecelltoanother.Severalcriteriashouldbefulfilledforasubstancetobeacceptedasaneurotransmitter.⑴Thesubstancemustbepresentwithinthepresynapticneuron.Clearly,achemicalcannotbesecretedfromapresynapticneuronunlessitispresentthere.Becauseelaboratebiochemicalpathwaysarerequiredtoproduceneurotransmitters,showingthattheenzymesandprecursorsrequiredtosynthesizethesubstancearepresentinpresynapticneuronsprovidesadditionalevidencethatthesubstanceisusedasatransmitter.⑵Thesubstancemustbereleasedinresponsetopresynapticdepolarization,andthereleasemustbeCa2+-dependent.⑶Specificreceptorsforthesubstancemustbepresentonthepostsynapticcell.Aneurotransmittercannotactonitstargetunlessspecificreceptorsforthetransmitterarepresentinthepostsynapticmembrane.Onewaytodemonstratereceptorsistoshowthatapplicationofexogenoustransmittermimicsthepost-synapticeffectofpresynapticstimulation.Amorerigorousdemonstrationistoshowthatspecificantagonistmolecules,whetherdeliveredthroughthecirculationorbyiontophoresis,mustblocktheeffectoftheputative('thoughttobe')transmitter.⑷Thephysiologicmodeofterminationofthetransmittereffectmustbeidentified,whetheritbebyenzymaticdegradationorbyactivetransportintotheparentneuronoradjacentneuroglialcells.5.2.CategoriesofNeurotransmittersThethreemajortypesofneurotransmittersinthebrainarethebiogenicamines,theaminoacids,andthepeptides.Recentdatahaveledtotheidentificationofatleastfourotherclassesofneurotransmitters—nucleotides,gases,eicosanoids,andanandamides.5.3.NeurotransmitterSynthesisandStorageThesynthesisofsmall-moleculeneurotransmittersoccurslocallywithinpresynapticterminals.Theenzymesneededtosynthesizethesetransmittersareproducedintheneuronalcellbodyandtransportedtothenerveterminalcytoplasm.Theprecursormoleculesrequiredtomakenewmoleculesofneurotransmitterareusuallytakenintothenerveterminalbytransportersfoundintheplasmamembraneoftheterminal.Theenzymessynthesizeneurotransmittersinthecytoplasmofthepresynapticterminalandthetransmittersarethenloadedintosynapticvesiclesviatransportersinthevesicularmembrane.Forsomesmall-moleculeneurotransmitters,thefinalstepsofsynthesisoccurinsidethesynapticvesicles.Mostsmall-moleculeneurotransmittersarepackagedinvesicles40to60nmindiameter,thecentersofwhichappearclearinelectronmicrographs;accordingly,thesevesiclesarereferredtoassmallclear-corevesicles.Neuropeptidesaresynthesizedinthecellbodyofaneuron,meaningthatthepeptideisproducedalongdistanceawayfromitssiteofsecretion.Tosolvethisproblem,peptide-filledvesiclesaretransportedalonganaxonanddowntothesynapticterminalviafastaxonaltransport.Neuropeptidesarepackagedintosynapticvesiclesthatrangefrom90to250nmindiameter.Thesevesiclesareelectron-denseinelectronmicrographs—hencetheyarereferredtoaslargedense-corevesicles.5.4.CoexistenceofDifferentNeurotransmittersItisnowclearthatmanytypesofneuronssynthesizeandreleasetwoormoredifferentneurotransmitters.Whenpeptideandsmall-moleculeneurotransmittersactasco-transmittersatthesamesynapse,theyaredifferentiallyreleasedaccordingtothepatternofsynapticactivity:low-frequencyactivityoftenreleasesonlysmallneurotransmitters,whereashigh-frequencyactivityisrequiredtoreleaseneuropeptidesfromthesamepresynapticterminals.5.5.NeurotransmitterReleaseReleaseoftransmitterfromaneuronistriggeredbythearrivalofapropagatednerveimpulseatitsterminals.Thiswaveofexcitationcausestheopeningofvoltage-gatedCa2+~channelsormobilizationofCa2+fromintracellularstores(e.g.theendoplasmicreticulum).Asaresult,thereisaphasicincreaseinfreeintracellularCa2+inregionsoftheterminaladjacenttothesiteoftransmitterrelease(the'activezone').Thesubsequentfusionofneurotransmitterstoragevesicleswiththeaxolemma,togetherwiththeextrusionoftheircontentsintothesynapse,isthoughttotakeabout100-200μs;thiscascadeisthereforefastenoughtoeffectrapidsignalingbetweenneurons.5.6.Receptor-MediatedModulationofTransmitterReleaseRegulationoftransmitterreleasedoesnotrestsolelyonthefrequencyatwhichnerveimpulsesreachtheterminals.Itisnowgenerallyacceptedthattherearereceptorsonnerveterminalswhich,whenactivatedbyreleasedtransmitter,attenuateitsfurtherrelease;thesepresynapticreceptorsareknownas'autoreceptors'.Manydifferenttypesofneuronsappeartohaveauto-receptors,includingthosethatreleaseacetylcholine,dopamine,GABA,5-HT,andhistamine.5.7.Ca2+-IndependentReleaseofTransmitterItisnowwellestablishedthattransmitterinthecytoplasmofneuronscanbereleasedbyaprocesswhichisnotdependentonCa2+.Formonoamines,thisisbestillustratedbytheactionsofamphetamineanditsanalogues.Studiesofarangeofsubstitutedamphetamineshaveconfirmedthatamphetamine-inducedreleaseof5-HTrepresentsareversedeffluxoftransmitteronthemembrane-boundcarrier.5.8.TerminationoftheActionofNeurotransmittersAfteraneurotransmitterhasbeensecretedintothesynapticcleft,itmustberemovedtoenablethepostsynapticcelltoengageinanothercycleofsynaptictransmission.Theremovalofneurotransmittersinvolvesdiffusionawayfromthepostsynapticreceptors,reuptakeintonerveterminalsorsurroundingglialcells,degradationbyspecificenzymes,oracombinationofthesemechanisms.Specifictransporterproteinsremovemostsmall-moleculeneurotransmitters(ortheirmetabolites)fromthesynapticcleft,ultimatelydeliveringthembacktothepresynapticterminalforreuse.6.NeurotransmitterReceptorsAllneurotransmittersexerttheireffectsbyactivatingmembrane-associatedproteinscalledreceptors.Whenreceptorsareligand-gatedionicchannels,theyareionotropicreceptors,whereasmetabotropicreceptorsgenerallyrefertoreceptorsthatarecoupledtoGproteinsandproduceamodificationoftheconcentrationofasecond,intracellularmessengerorthemodulationofanionicchannel.Eachneurotransmitterstimulatesanarrayofreceptors,therebyelicitinganumberofpostsynapticresponses.Moreover,responsestoagivenneurotransmittercanbemodifiedasaresultofthesimultaneousactivationofreceptorsforanotherneurotransmitteronthesametargetcellorofthepastactivityofthetargetcell.7.PostsynapticPotentialsPostsynapticpotentialsarecalledexcitatorypostsynapticpotentials(orEPSPs)iftheyincreasethelikelihoodofapostsynapticactionpotentialoccurring,andinhibitorypostsynapticpotentials(orIPSPs)iftheydecreasethislikelihood.8.SummationofSynapticPotentialsNeuronsinthecentralnervoussystemaretypicallyinnervatedbythousandsofsynapses,andthepostsynapticpotentialsproducedbyeachactivesynapsecansumtogether—inspaceandintime—todeterminethebehaviorofthepostsynapticneuron.ThesummationofEPSPsandIPSPsbyapostsynapticneuronpermitsaneurontointegratetheelectricalinformationprovidedbyalltheinhibitoryandexcitatorysynapsesactingonitatanymoment.三、重點、難點提示和教學手段（一）重點：掌握神經細胞之間信息傳遞的方式、步驟和涉及的結構；掌握幾種與精神障礙有密切關系的神經遞質。（二）難點：突觸傳遞過程及突觸電位的整合。（三）教學手段：多媒體教學，盡量運用圖片和錄像增加學生的感性認識。雙語教學，講授法（結合提問、臨床病例等進行啟發(fā)式教學等）。（四）教具：多媒體電腦、多媒體投影儀、投影屏幕、多媒體課件、激光筆等四、思考與練習1．神經細胞之間是怎樣進行信息傳遞的？2．神經細胞信息傳遞的電-化學轉變是怎樣實現(xiàn)的？3．有哪些可能的方式能影響神經細胞之間的信息傳遞？第三章神經元內信號傳遞途徑一、學習目的通過本章的學習，掌握神經元內信號傳遞途徑，了解神經元內信號傳遞的功能。本章計劃2學時。二、課程內容1.OverviewTheintracellularprocessingtypicallybeginswhenextracellularchemicalsignals,suchasneurotransmitters,hormones,andtrophicfactors,bindtospecificreceptorslocatedeitheronthesurfaceorwithinthecytoplasmornucleusofthetargetcells.SuchbindingactivatesthereceptorsandinsodoingstimulatescascadesofintracellularreactionsinvolvingGTP-bindingproteins,secondmessengermolecules,proteinkinases,ionchannels,andmanyothereffectorproteinswhosemodulationtemporarilychangesthephysiologicalstateofthetargetcell.Thesesameintracellularsignaltransductionpathwayscanalsocauselonger-lastingchangesbyalteringthetranscriptionofgenes,thusaffectingtheproteincompositionofthetargetcellsonamorepermanentbasis.2.FormsofChemicalSignalingChemicalsignalingisnotlimitedtosynapses.Otherwell-characterizedformsofchemicalcommunicationincludeparacrinesignaling,whichactsoveralongerrangethansynaptictransmissionandinvolvesthesecretionofchemicalsignalsontoagroupofnearbytargetcells,andendocrinesignaling,whichreferstothesecretionofhormonesintothebloodstreamwheretheycanaffecttargetsthroughoutthebody.3.TheFunctionofIntraneuronalSignalingAgeneraladvantageofchemicalsignalinginbothintercellularandintracellularcontextsissignalamplification.Withtheaidoftheseinternalsignalingpathways,thepostsynapticneuronpartakesactivelyinamplifyingormutingtheinitialsignalconveyedbyaparticularreceptorandisnotrelegatedtothesubservientstatusofatotallypassivepartnerinrespondingtotheseexternalcues.Theinternalsignalingpathwaysempowerneuronstoshapetheirresponsestoincomingstimuli;collectively,thesechangesinensemblesofneuronsareofparamountimportanceinenablingthenervoussystemtoadapttoitsenvironmentandlearnfromexperience.4.TheActivationofSignalingPathwaysThemolecularcomponentsofthesesignaltransductionpathwaysarealwaysactivatedbyachemicalsignalingmolecule.Suchsignalingmoleculescanbegroupedintothreeclasses:cell-impermeant,cell-permeant,andcell-associatedsignalingmolecules.Cell-impermeantsignalingmoleculestypicallybindtoreceptorsassociatedwithcellmembranes.Hundredsofsecretedmoleculeshavenowbeenidentified,includingtheneurotransmitters,proteinssuchasneurotrophicfactors,andpeptidehormonessuchasinsulin.Cell-permeantsignalingmoleculescancrosstheplasmamembranetoactdirectlyonreceptorsthatareinsidethecell.Examplesincludenumeroussteroid(glucocorticoids,estradiol,andtestosterone)andthyroidhormones.Thethirdgroupofchemicalsignalingmolecules,cell-associatedsignalingmolecules,arearrayedontheextracellularsurfaceoftheplasmamembrane.Examplesincludeproteinssuchastheintegrinsandneuralcelladhesionmoleculesthatinfluenceaxonalgrowth.5.ReceptorTypesChannel-linkedreceptors(alsocalledligand-gatedionchannels)havethereceptorandtransducingfunctionsaspartofthesameproteinmolecule.G-protein-coupledreceptorsregulateintracellularreactionsbyanindirectmechanisminvolvinganintermediatetransducingmolecule,calledtheGTP-bindingproteins(orG-proteins).Enzyme-linkedreceptorsalsohaveanextracellularbindingsiteforchemicalsignals.Intracellularreceptorsareactivatedbycell-permeantorlipophilicsignalingmolecules.6.G-ProteinsTherearetwogeneralclassesofGTP-bindingprotein.HeterotrimericG-proteinsarecomposedofthreedistinctsubunits(α,β,andγ).ThesecondclassofGTP-bindingproteinsaremonomericG-proteins(alsocalledsmallG-proteins).ThesemonomericGTPasesalsorelaysignalsfromactivatedcellsurfacereceptorstointracellulartargetssuchasthecytoskeletonandthevesicletraffickingapparatusofthecell.7.G-ProteinsTargetsActivatedG-proteinsalterthefunctionofmanydownstreameffectors.Mostoftheseeffectorsareenzymesthatproduceintracellularsecondmessengers.Effectorenzymesincludeadenylylcyclase,guanylylcyclase,phospholipaseC,andothers.8.SecondMessengers8.1.Calcium8.2.Cyclicnucleotides8.3.DiacylglycerolandIP39.SecondMessengerTargets:ProteinKinasesandPhosphatasesTheactivityofproteinkinasesandphosphatasescanberegulatedeitherbysecondmessengers,suchascAMPorCa2+,orbyextracellularchemicalsignals,suchasgrowthfactors.Althoughthousandsofproteinkinasesareexpressedinthebrain,arelativelysmallnumberfunctionasregulatorsofneuronalsignaling.cAMP-dependentproteinkinase(PKA)Ca2+/calmodulin-dependentproteinkinasetypeII(CaMKII)ProteinkinaseC(PKC)ProteintyrosinekinasesMitogen-activatedproteinkinase(MAPK)10.NuclearSignalingIntracellularsignaltransductioncascadesregulategeneexpressionbyconvertingtranscriptionalactivatorproteinsfromaninactivestatetoanactivestateinwhichtheyareabletobindtoDNA.Thisconversioncomesaboutinseveralways.Thekeyactivatorproteinsandthemechanismsthatallowthemtoregulategeneexpressioninresponsetosignalingeventsarebrieflysummarizedinthefollowingsections.CREBThecAMPresponseelementbindingprotein,usuallyabbreviatedCREB,isaubiquitoustranscriptionalactivator.Nuclearreceptorsc-fosprotein三、重點、難點提示和教學手段（一）重點：神經元內信號傳遞途徑。（二）難點：第二信使及第二信使作用對象：蛋白激酶和磷酸酶。（三）教學手段：多媒體教學，盡量運用圖片和錄像增加學生的感性認識。雙語教學，講授法（結合提問、臨床病例等進行啟發(fā)式教學等）。（四）教具：多媒體電腦、多媒體投影儀、投影屏幕、多媒體課件、激光筆等四、思考與練習1．神經元內信號傳遞的步驟及功能意義。2．名詞解釋：神經元的基因表達第四章神經遞質一、學習目的通過本章的學習，理解神經遞質在正常和異常精神活動中的作用，掌握乙酰膽堿、多巴胺、去甲腎上腺素、5-羥色胺、γ-氨基丁酸、谷氨酸六種主要神經遞質的腦內通路、合成與代謝、受體，了解上述主要神經遞質的精神病理學意義。本章計劃4學時。二、課程內容1.Acetylcholine(ACh)1.1.CholinergicPathwaysTwolargeclustersofcholinergicprojectionneuronsarefoundwithinthebrain:thebasalforebraincomplexandthemesopontinecomplex.Thebasalforebraincomplexprovidesthevastmajorityofthecholinergicinnervationtothenonstriataltelencephalon.Themesopontinecomplexconsistsofcholinergicneuronswithinthepedunculopontineandlaterodorsaltegmentalnucleiofthemidbrainandpons.Regionsinnervatedbytheseprojectionsincludethelateralhypothalamus,thalamus,tectum,substantianigra,raphenuclei,locusceruleus,andcranialnervenuclei.1.2.AcetylcholineLifeCycleAcetylcholineissynthesizedinnerveterminalsfromtheprecursorsacetylcoenzymeA(acetylCoA,whichissynthesizedfromglucose)andcholine,inareactioncatalyzedbycholineacetyltransferase(CAT).ReleasedAChisbrokendownbymembrane-boundacetylcholinesterase(AChE).1.3.CholinergicReceptorsTwomajorclassesofcholinergicreceptorsexist:Gprotein–coupledmuscarinicreceptorsandnicotinicligand-gatedionchannels.1.4.AcetylcholineandDrugsThemostcommonuseofanticholinergicdrugsinpsychiatryisasatreatmentofthemotorabnormalitiescausedbytheuseofclassicantipsychoticdrugs.Blockadeofmuscariniccholinergicreceptorsisacommonpharmacodynamiceffectofmanypsychotropicdrugs.Blockadeofthosereceptorsleadstothecommonlyseensideeffectsofblurredvision,drymouth,constipation,anddifficultyininitiatingurination.ExcessiveblockadeofCNScholinergicreceptorscausesconfusionanddelirium.Drugsthatincreasecholinergicactivitybyblockingbreakdownbyacetylcholinesterase(forexample,donepezil)havebeenshowntobeeffectiveinthetreatmentofdementiaoftheAlzheimer'stype.1.5.AcetylcholineandPsychopathologyThemostcommonassociationwithacetylcholineisdementiaoftheAlzheimer'stypeandotherdementias.Anticholinergicagentscanimpairlearningandmemoryinnormalpeople.Withtherecentidentificationoftheproteinstructuresofthevariousmuscarinicandnicotinicreceptors,manyresearchersareworkingonspecificmuscarinicandnicotinicagoniststhatmayprovetobeofsomebenefitinthetreatmentofdementiaoftheAlzheimer'stype.Acetylcholinemayalsobeinvolvedinmoodandsleepdisorders.2.Dopamine(DA)2.1.DopaminePathwaysDopamineneuronsarewidelydistributed,re