醫(yī)學(xué)神經(jīng)生物學(xué)：02 突觸傳遞和調(diào)控

神經(jīng)元的電活動與突觸傳遞什么是神經(jīng)元電活動？如何形成的？什么是突觸？為什么突觸傳遞在神經(jīng)科學(xué)研究中如此重要？神經(jīng)元電活動的基礎(chǔ)

——離子通道離子通道的一般特征物理特征離子選擇性通道激活模式開放和關(guān)閉物理特性胞外胞內(nèi)胞外－－－－－－－－－－＋＋＋＋＋＋＋＋＋＋＋＋＋＋跨膜孔道膜內(nèi)和膜外側(cè)擴大形成腔膜內(nèi)段縮窄有門控結(jié)構(gòu)通道的離子選擇性

陽離子選擇性Na+

K+

Ca2+陰離子選擇性Cl-陽離子一般特殊：某些通道特異性小，甚至允許小的有機物質(zhì)通過。細胞內(nèi)環(huán)境的離子穩(wěn)態(tài)細胞膜的隔離通道的離子選擇性通道的選擇性是相對的，例如鈉通道不但對鈉離子通透，對銨（NH4+）也通透；甚至對鉀離子也稍有通透。通道離子選擇性和電壓感受的機制電壓激活模式牽張激活模式配體激活通道通道激活模式注意以上分類并非絕對的；例如鈣激活鉀通道也對電壓變化敏感，有些電壓激活通道也對細胞內(nèi)配體敏感！離子通道的分類選擇性陽離子通道非選擇性陽離子通道陰離子通道跨膜轉(zhuǎn)運系統(tǒng)鈉－鉀泵鈣泵鈉－鈣泵氯離子通道鉀離子通道鈉離子通道鈣離子通道谷氨酸受體陽離子通道N2型乙酰膽堿受體陽離子通道嘌呤受體陽離子通道5－HT3受體陽離子通道軸突的終端為軸突末梢，它終止于另一神經(jīng)元或效應(yīng)器，與它們形成突觸。

軸突末梢(axonterminals)每個神經(jīng)元大約會有1萬個突觸突觸（synapse）定義：一個神經(jīng)元與另一個神經(jīng)元相接觸的部位叫做突觸。突觸是神經(jīng)元之間在功能上發(fā)生聯(lián)系的部位，也是信息傳遞的關(guān)鍵部位。電突觸1μm化學(xué)突觸

人類CNS內(nèi)大約有1014個。脊髓前角神經(jīng)元平均有2000個突觸聯(lián)系，皮層神經(jīng)元則因為3萬個。突觸的分類①軸突-樹突式突觸②軸突-胞體式突觸③軸突-軸突式突觸化學(xué)突觸的結(jié)構(gòu)化學(xué)突觸的結(jié)構(gòu)突觸傳遞相關(guān)受體突觸的傳遞過程興奮傳至神經(jīng)末梢↓突觸前膜去極化↓前膜電壓門控式Ca2＋通道開放↓Ca2＋進入突觸前膜↓神經(jīng)遞質(zhì)通過出胞作用釋放到突觸間隙↓遞質(zhì)作用于突觸后膜的特異性受體或化學(xué)門控式通道↓突觸后膜上某些離子通道通透性改變↓某些離子進入突觸后膜↓后膜去極化或超極化（突觸后電位）電-化學(xué)-電的傳遞過程FM143染料突觸的傳遞過程的動態(tài)觀測突觸后電流:突觸前釋放神經(jīng)遞質(zhì)激活突觸后膜相應(yīng)受體引起的突觸后膜的電流變化。去極化的電流變化稱作興奮性突出后電流，超極化的電流變化稱作抑制性突觸后電流。突觸后電位參與動作電位的形成Threesynapticjunctions,eachreleaseanexcitatoryneurotransmitterspatialsummationThreesynapticjunctions,

2arestimulatory,1isinhibitory.

spatialsummation軸突動作電位突觸前囊泡釋放突觸后膜受體激活突觸后電位突觸后膜受體和離子通道分布和類型其他不同突觸活動信息處理軸突局部離子通道分布，類型以及突觸活動突觸前膜離子通道分布和類型突觸前膜離子通道分布和類型突觸囊泡施放相關(guān)蛋白的功能軸突局部環(huán)境對信息的影響和調(diào)控軸突局部離子通道分布，類型軸突局部離子通道分布，類型對信息傳遞的影響NATURE|Vol465|24June2010NATURE|Vol465|24June2010膜電位超極化局部突觸活動對信息傳遞的影響突觸前膜離子通道分布和類型以及突觸囊泡施放相關(guān)蛋白的功能Neuron59,September25,2008突觸囊泡釋放機制mEPPsprovideevidencethatsynaptictransmissionisquantal(vesicular)SnaptobrebinSNAP-25SyntaxinSynaptotagmin-SNAPSNSFSynapsinI突觸后膜受體和離子通道分布和類型Activity-dependenttraffickingofK+channels.(a)IllustrationdepictingthetranslocationofseveralK+channelsinresponsetocommonformsofneuronalplasticity.ExtrasynapticKV4.2channelsandKCa2.2channelslocatednearthepostsynapticdensity(PSD)areinternalizedduringLTP,requiringCa2+influxandPKAactivation(1);Kir3.2channelsareinsertedintothesynapseduringdepotentiationviaCa2+influxandproteinphosphatase-1(PP1)activation(2);andKV2.1channelsdeclusteruponglutamatestimulation,aprocessdependentonCa2+influxandproteinphosphatase-2B(PP2B)activation(3).Glialglutamatetransporters(GLT)alsoinfluenceKv2.1dephosphorylationthroughtheirregulationofextrasynapticNMDAR–Kv2.1channelcouplingTrendsinNeurosciencesVol.33No.7學(xué)習(xí)記憶的基礎(chǔ)——LTP和LTD信息流突觸傳遞的逆向調(diào)節(jié)信息流Neuron63,July30,2009生命的本質(zhì)是運動電突觸電突觸的結(jié)構(gòu)電突觸的分布和功能Electricalsynapse：

nervoussystem，cardiacmuscle,smoothmuscleandliver。電鏡發(fā)現(xiàn)：哺乳類動物的大腦皮層感覺區(qū)星狀cell,小腦皮層藍細胞與星狀細胞，視網(wǎng)膜水平細胞與雙極細胞，嗅球的僧帽細胞以及神經(jīng)膠質(zhì)細胞均存在著電突觸。Function：

inexcitablecell:電突觸雙向快速傳遞，傳遞空間減少，則傳遞更有效，突觸靈活性增加，有利于機能相似的細胞進行同步活動。低電阻通路還可調(diào)節(jié)細胞間小分子量物質(zhì)的轉(zhuǎn)移。而細胞間的化學(xué)突觸傳遞易于受到代謝障礙的明顯影響，而電突觸具有較大的耐受力。

innonexcitablecell:它是和生長代謝的控制，胚胎的發(fā)育及分化等現(xiàn)象有關(guān)。它可運輸某些代謝產(chǎn)物和營養(yǎng)物質(zhì)。電突觸突觸電位兩個膜緊密接觸，離子通道相通離子YuYC*#,HeS*#,ChenS,FuY,BrownKN,YaoXH,MaJ,GaoKP,SosinskyGE,HuangK,ShiSH#

(2012)Preferentialelectricalcouplingregulatesneocorticallineage-dependentmicrocircuitassembly.

Nature

486:113-117膠質(zhì)細胞對突觸傳遞的影響膠質(zhì)細胞：腦中數(shù)量最多的細胞神經(jīng)元：目前認為是腦功能實現(xiàn)的主體血管，結(jié)締組織等：營養(yǎng)保護作用膠質(zhì)細胞的數(shù)量是神經(jīng)元的十倍！

人腦中有約1000億個神經(jīng)元似乎膠質(zhì)細胞更為重要但是對于大腦的獨特功能來說，神經(jīng)元更為重要！原因：神經(jīng)元能夠感知環(huán)境的變化并將信息傳遞給其它神經(jīng)元指令機體作出反應(yīng)。膠質(zhì)細胞其隔離、支持、保護、營養(yǎng)神經(jīng)元的作用但是越來越多的研究正使我們對膠質(zhì)細胞的功能發(fā)生全新的改變。有人研究愛因斯坦的大腦后發(fā)現(xiàn)其大腦的膠質(zhì)細胞量顯著高于普通人70％?。?！新的研究已經(jīng)證明膠質(zhì)細胞在神經(jīng)元信息處理過程中有著有著重要作用。Mechanismsregulatingglialglutamatetransporterlevels.Astrocytesplayanactiveroleintheremovalofneurotransmittersfromthesynapseviatransportmechanisms.Glutamatetransportersinastrocytesenvelopingsynapseslimitglutamatespilloverandmodulatesynaptictransmissionandplasticity.PresynapticterminalsinduceinastrocytesthetranscriptionalactivationofGLT1,viaKBBP.TheEphA4/ephrinA3neuron–astrocytecommunicationlimitsglutamatetransporterabundance,therebycontributingtomodulationofsynapticplasticity.Thetripartitesynapse.Whenneurotransmittersarereleasedfromthepresynapticneuron(1),astrocyticmetabotropicglutamatereceptors(mGluRs)areactivatedleadingtoariseinCa2+ionsintheastrocyte(2)andthereleaseofneuroactivesubstancesfromastrocytes.Thesegliotransmittersactbackontheneuronandregulatepresynapticfunctionormodulatetheresponseofthepostsynapticneuron.(a)Glutamatereleasedfromastrocytes(3)canactpostsynapticallyonNMDARstherebyenhancingexcitabilityoftheneuronandsynchronizingneuronalactivity(4);glutamatealsoactspresynapticallyonmGluRsorNMDARstherebyincreasingtransmitterreleaseprobability(Pr)(5).(b)ThereleaseofD-serine(3)actsontheglycinebindingsiteofNMDARsandcanregulatesynapticplasticity(4).AstrocyticATPrelease(5)contributestosynapticscalingbyactingonpurinergicP2Xreceptors(6).Adenosine,aproductofATPrelease(7),activatespresynapticA1Rs(8)andsuppressesglutamaterelease.Interplaybetweenastrocytes,neuronsandthevasculature.(a)Astrocytesareconnectedviagapjunctionsandformnetworksthatassociatewithseveral,possiblymanysynapses.Astrocyticnetworksareconsideredactiveelementsofneuralcircuits,exhibitingcalciumexcitabilityandprocessinginformation.(b)Theneurovascularunit.Astrocytes,eitherasindividuals(asshownhere)oraspartofalargernetwork,couplesynapsesandbloodcapillariestocontrolcognitivefunctions.Theresponsecharacteristicsofindividualastrocytesandneuronsinthevisualcortexarecloselycoupled.沉默突觸（Silencesynapse）沉默是金！Silenceisgold！whoseexistencehasbeenrecognizedlongago(Mendell1984）普遍認為，在神經(jīng)元的發(fā)育早期，大多數(shù)突觸后膜上只含NMDA受體而不含AMPA受體。隨著神經(jīng)系統(tǒng)的發(fā)育成熟，AMPA受體的轉(zhuǎn)運上膜后才有大量功能性突觸的產(chǎn)生。研究者也習(xí)慣的把只含NMDA受體的突觸定義為沉默突觸（silentsynapse）。概念暫時沒有信息傳遞功能的突觸InvolvementofpresynapticallyorpostsynapticallysilentsynapsesinLTPmaintenance.PresynapticterminalscontactingpostsynapticspinesareschematicallyrepresentedbeforeandafterLTP.(a)Inpresynapticallysilentsynapses(yellow)withlowreleaseprobability(Pr)noresponsescanbedetectedbeforeLTP(uppertrace)inspitetheexpressionoffunctionalAMPARsandNMDARsonthesubsynapticmembrane.AfterLTP,theincreasedPrleadstotheappearanceofsynapticresponses(afterLTP,uppertrace).InasynapsewithlowPr(green)beforeLTP(lowertrace),Prcanbecomecloserto1asaresultofLTPinductionsothatnofailuresappearafterLTP(lowertrace).(b)I