1、會(huì)計(jì)學(xué)1突觸傳遞和調(diào)控突觸傳遞和調(diào)控第2頁(yè)/共65頁(yè)第3頁(yè)/共65頁(yè)胞外胞外胞內(nèi)胞內(nèi)胞外胞外跨膜跨膜孔道孔道膜內(nèi)和膜外側(cè)擴(kuò)大形成腔膜內(nèi)和膜外側(cè)擴(kuò)大形成腔膜內(nèi)段縮窄有門控結(jié)構(gòu)膜內(nèi)段縮窄有門控結(jié)構(gòu)第4頁(yè)/共65頁(yè)陽(yáng)離子選擇性陽(yáng)離子選擇性Na+ K+ Ca2+陰離子選擇性陰離子選擇性Cl-陽(yáng)離子陽(yáng)離子一一般般特殊：某些通道特異性小，甚至允許小的有機(jī)物質(zhì)通過(guò)。特殊：某些通道特異性小，甚至允許小的有機(jī)物質(zhì)通過(guò)。細(xì)胞內(nèi)環(huán)境的離細(xì)胞內(nèi)環(huán)境的離子穩(wěn)態(tài)子穩(wěn)態(tài)細(xì)胞膜的細(xì)胞膜的隔離隔離通道的離子選擇性通道的離子選擇性陰離子通道的特異性較小，它們之所以稱為陰離子通道的特異性較小，它們之所以稱為Cl-通道是因?yàn)橥ǖ朗且?/p>

2、為Cl-是生物溶液的主要陰離子是生物溶液的主要陰離子通道的選擇性是相對(duì)的，例如鈉通道不但對(duì)鈉離子通透，對(duì)通道的選擇性是相對(duì)的，例如鈉通道不但對(duì)鈉離子通透，對(duì)銨（銨（NH4+）也通透；甚至對(duì)鉀離子也稍有通透。）也通透；甚至對(duì)鉀離子也稍有通透。第5頁(yè)/共65頁(yè)胞外胞外胞內(nèi)胞內(nèi)60mv通道離子選擇性和電壓感受的機(jī)制通道離子選擇性和電壓感受的機(jī)制第6頁(yè)/共65頁(yè)第7頁(yè)/共65頁(yè)注意注意以上分類并非絕對(duì)的；以上分類并非絕對(duì)的；例如鈣激活鉀通道例如鈣激活鉀通道也對(duì)電壓變化敏感，也對(duì)電壓變化敏感，有些電壓激活通道有些電壓激活通道也對(duì)細(xì)胞內(nèi)配體敏感！也對(duì)細(xì)胞內(nèi)配體敏感！第8頁(yè)/共65頁(yè)選擇性陽(yáng)離子通道選擇性陽(yáng)

3、離子通道非選擇性陽(yáng)離子通非選擇性陽(yáng)離子通道道陰離子通道陰離子通道跨膜轉(zhuǎn)運(yùn)系統(tǒng)跨膜轉(zhuǎn)運(yùn)系統(tǒng)鈉鉀泵鈉鉀泵鈣泵鈣泵鈉鈣泵鈉鈣泵氯離子通道氯離子通道鉀離子通道鉀離子通道鈉離子通道鈉離子通道鈣離子通道鈣離子通道谷氨酸受體陽(yáng)離子通道谷氨酸受體陽(yáng)離子通道N2型乙酰膽堿受體陽(yáng)離子通道型乙酰膽堿受體陽(yáng)離子通道嘌呤受體陽(yáng)離子通嘌呤受體陽(yáng)離子通道道5HT3受體陽(yáng)離子通受體陽(yáng)離子通道道第9頁(yè)/共65頁(yè)門控離子通道門控離子通道化學(xué)門控離子通道化學(xué)門控離子通道鈉通道鈉通道鈣通道鈣通道鉀通道鉀通道遞質(zhì)遞質(zhì)離子離子代謝物代謝物非門控離子通道非門控離子通道電壓門控離子通電壓門控離子通道道離子通道的分類（門控方式）離子通道的分類

4、（門控方式）第10頁(yè)/共65頁(yè)3:1生電性生電性生電性生電性生電性生電性第11頁(yè)/共65頁(yè)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 (axon terminals)每個(gè)神經(jīng)每個(gè)神經(jīng)元大約會(huì)元大約會(huì)有有1萬(wàn)個(gè)突萬(wàn)個(gè)突觸觸第12頁(yè)/共65頁(yè)第13頁(yè)/共65頁(yè)電突觸電突觸1 m化學(xué)突觸化學(xué)突觸第14頁(yè)/共65頁(yè)第15頁(yè)/共65頁(yè)第16頁(yè)/共65頁(yè)突觸傳遞相關(guān)受體突觸傳遞相關(guān)受體第17頁(yè)/共65頁(yè)突觸后電流突觸后電流: 突觸前釋放神經(jīng)遞質(zhì)激活突觸突觸前釋放神經(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。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

5、興奮性突出后電流，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。超極化的電流變化稱作抑制性突觸后電流。第18頁(yè)/共65頁(yè)第19頁(yè)/共65頁(yè)第20頁(yè)/共65頁(yè)突觸后電位參與動(dòng)作電位的形成突觸后電位參與動(dòng)作電位的形成第21頁(yè)/共65頁(yè)軸突動(dòng)作電位軸突動(dòng)作電位突觸前囊泡釋放突觸前囊泡釋放突觸后膜受體激活突觸后膜受體激活突觸后電位突觸后電位突觸后膜受體和離子通道分布和類型突觸后膜受體和離子通道分布和類型其他不同突觸活動(dòng)其他不同突觸活動(dòng)信息處理信息處理軸突局部離子通道分布，軸突局部離子通道分布，類型以及突觸活動(dòng)類型以及突觸活動(dòng)突觸前膜離子通道分布和類型突觸前膜離子通道分布和

6、類型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)蛋白的功能突觸囊泡施放相關(guān)蛋白的功能第22頁(yè)/共65頁(yè)軸突局部環(huán)境對(duì)信息的影響和調(diào)控軸突局部環(huán)境對(duì)信息的影響和調(diào)控第23頁(yè)/共65頁(yè)軸突局部離子通道分布，類型軸突局部離子通道分布，類型第24頁(yè)/共65頁(yè)軸突局部離子通道分布，類型對(duì)信息傳遞的影響軸突局部離子通道分布，類型對(duì)信息傳遞的影響第25頁(yè)/共65頁(yè)NATURE| Vol 465|24 June 2010第26頁(yè)/共65頁(yè)NATURE| Vol 465|24 June 2010第27頁(yè)/共65頁(yè)膜電位超極化局部突觸活動(dòng)對(duì)信息傳遞的影響局部突觸活動(dòng)對(duì)信息傳遞的影響第28頁(yè)

7、/共65頁(yè)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以及突觸囊泡施放相關(guān)蛋白的功能以及突觸囊泡施放相關(guān)蛋白的功能第29頁(yè)/共65頁(yè)第30頁(yè)/共65頁(yè)Neuron 59, September 25, 2008第31頁(yè)/共65頁(yè)突觸囊泡釋放機(jī)制突觸囊泡釋放機(jī)制第32頁(yè)/共65頁(yè)mEPPs provideevidence thatsynaptictransmission isquantal(vesicular)第33頁(yè)/共65頁(yè)SnaptobrebinSNAP-25SyntaxinSynaptotagmin -SNAPSNSFSynapsin I第34頁(yè)/共65頁(yè)第35頁(yè)/共65頁(yè)Acti

8、vity-dependent trafficking of K+ channels. (a) Illustration depicting the translocation of several K+ channels in response to common forms of neuronal plasticity. Extrasynaptic KV4.2 channels and KCa2.2 channels located near the postsynaptic density (PSD) are internalized during LTP, requiring Ca2+

9、influx and PKA activation (1); Kir3.2 channels are inserted into the synapse during depotentiation via Ca2+ influx and protein phosphatase-1 (PP1) activation (2); and KV2.1 channels decluster upon glutamate stimulation, a process dependent on Ca2+ influx and protein phosphatase-2B (PP2B) activation

10、(3). Glial glutamate transporters (GLT) also influence Kv2.1 dephosphorylation through their regulation of extrasynaptic NMDARKv2.1 channel couplingTrends in Neurosciences Vol.33 No.7第36頁(yè)/共65頁(yè)動(dòng)作電位在突觸后神經(jīng)元產(chǎn)生：EPSP在軸突的始段達(dá)到-52mV左右時(shí)，就可以引發(fā)動(dòng)作電位。始段爆發(fā)的動(dòng)作電位向兩個(gè)方向擴(kuò)布。逆向擴(kuò)布的動(dòng)作電位將刷新神經(jīng)元胞體的狀態(tài)。 第37頁(yè)/共65頁(yè)信息流突觸傳遞的逆向調(diào)節(jié)突觸傳

11、遞的逆向調(diào)節(jié)信息流第38頁(yè)/共65頁(yè)Neuron 63, July 30, 2009第39頁(yè)/共65頁(yè)第40頁(yè)/共65頁(yè)第41頁(yè)/共65頁(yè)第42頁(yè)/共65頁(yè)第43頁(yè)/共65頁(yè)Electrical synapse： nervous system，cardiac muscle,smooth muscle and liver。 電鏡發(fā)現(xiàn)：哺乳類動(dòng)物的大腦皮層感覺(jué)區(qū)星狀電鏡發(fā)現(xiàn)：哺乳類動(dòng)物的大腦皮層感覺(jué)區(qū)星狀cell,cell,小腦皮層小腦皮層藍(lán)細(xì)胞與星狀細(xì)胞，視網(wǎng)膜水平細(xì)胞與雙極細(xì)胞，嗅球的僧帽細(xì)胞藍(lán)細(xì)胞與星狀細(xì)胞，視網(wǎng)膜水平細(xì)胞與雙極細(xì)胞，嗅球的僧帽細(xì)胞以及神經(jīng)膠質(zhì)細(xì)胞均存在著電突觸。以及神經(jīng)膠質(zhì)

12、細(xì)胞均存在著電突觸。Function： in excitable cell:電突觸雙向快速傳遞，傳遞空間減少，則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(jī)能相似的細(xì)胞進(jìn)行傳遞更有效，突觸靈活性增加，有利于機(jī)能相似的細(xì)胞進(jìn)行同步活同步活動(dòng)動(dòng)。低電阻通路還可。低電阻通路還可調(diào)節(jié)細(xì)胞間小分子量物質(zhì)的轉(zhuǎn)移調(diào)節(jié)細(xì)胞間小分子量物質(zhì)的轉(zhuǎn)移。而細(xì)胞間的。而細(xì)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較大的耐受力。耐受力。 in nonexcitable cell:它是和生長(zhǎng)代謝的控制，胚胎的發(fā)育及它是和生長(zhǎng)

13、代謝的控制，胚胎的發(fā)育及分化等現(xiàn)象有關(guān)。它可運(yùn)輸某些代謝產(chǎn)物和營(yíng)養(yǎng)物質(zhì)。分化等現(xiàn)象有關(guān)。它可運(yùn)輸某些代謝產(chǎn)物和營(yíng)養(yǎng)物質(zhì)。第44頁(yè)/共65頁(yè)第45頁(yè)/共65頁(yè)電突觸突觸電位電突觸突觸電位兩個(gè)膜緊密接觸，離子通道相通兩個(gè)膜緊密接觸，離子通道相通離子離子第46頁(yè)/共65頁(yè)第47頁(yè)/共65頁(yè)第48頁(yè)/共65頁(yè)第49頁(yè)/共65頁(yè)第50頁(yè)/共65頁(yè)第51頁(yè)/共65頁(yè)第52頁(yè)/共65頁(yè)Mechanisms regulating glial glutamate transporter levels. Astrocytes play an active role in the removal of neurot

14、ransmitters from the synapse via transport mechanisms. Glutamate transporters in astrocytes enveloping synapses limit glutamate spillover and modulate synaptic transmission and plasticity. Presynaptic terminals induce in astrocytes the transcriptional activation of GLT1, via KBBP. The EphA4/ephrinA3

15、 neuronastrocyte communication limits glutamate transporter abundance, thereby contributing to modulation of synaptic plasticity.第53頁(yè)/共65頁(yè)The tripartite synapse. When neurotransmitters are released from the presynaptic neuron (1), astrocytic metabotropic glutamate receptors (mGluRs) are activated le

16、ading to a rise in Ca2+ ions in the astrocyte (2) and the release of neuroactive substances from astrocytes. These gliotransmitters act back on the neuron and regulate presynaptic function or modulate the response of the postsynaptic neuron. (a) Glutamate released from astrocytes (3) can act postsyn

17、aptically on NMDARs thereby enhancing excitability of the neuron and synchronizing neuronal activity (4); glutamate also acts presynaptically on mGluRs or NMDARs thereby increasing transmitter release probability (Pr) (5). (b) The release of D-serine (3) acts on the glycinebinding site of NMDARs and

18、 can regulate synaptic plasticity (4). Astrocytic ATP release (5) contributes to synaptic scaling by acting on purinergic P2X receptors (6). Adenosine, a product of ATP release (7), activates presynaptic A1Rs (8) and suppresses glutamate release.第54頁(yè)/共65頁(yè)Interplay between astrocytes, neurons and the

19、 vasculature. (a) Astrocytes are connected via gap junctions and form networks that associate with several, possibly many synapses. Astrocytic networks are considered active elements of neural circuits, exhibiting calcium excitability and processing information. (b) The neurovascular unit. Astrocyte

20、s, either as individuals (as shown here) or as part of a larger network, couple synapses and blood capillaries to control cognitive functions. The response characteristics of individual astrocytes and neurons in the visual cortex are closely coupled.第55頁(yè)/共65頁(yè)沉默是金！Silence is gold！whose existence has

21、been recognized long ago (Mendell 1984）第56頁(yè)/共65頁(yè)普遍認(rèn)為，在神經(jīng)元的發(fā)育早期，大多數(shù)突觸后膜普遍認(rèn)為，在神經(jīng)元的發(fā)育早期，大多數(shù)突觸后膜上只含上只含NMDA受體而不含受體而不含AMPA受體。隨著神經(jīng)系統(tǒng)受體。隨著神經(jīng)系統(tǒng)的發(fā)育成熟，的發(fā)育成熟，AMPA受體的轉(zhuǎn)運(yùn)上膜后才有大量功能受體的轉(zhuǎn)運(yùn)上膜后才有大量功能性突觸的產(chǎn)生。研究者也習(xí)慣的把只含性突觸的產(chǎn)生。研究者也習(xí)慣的把只含NMDA受體的受體的突觸定義為沉默突觸（突觸定義為沉默突觸（silent synapse）。）。 概念概念暫時(shí)沒(méi)有信息傳遞功能的突觸第57頁(yè)/共65頁(yè)第58頁(yè)/共65頁(yè)Invo

22、lvement of presynaptically or postsynaptically silent synapses in LTP maintenance. Presynaptic terminals contacting postsynapticspines are schematically represented before and after LTP. (a) In presynaptically silent synapses (yellow) with low release probability (Pr) noresponses can be detected bef

23、ore LTP (upper trace) in spite the expression of functional AMPARs and NMDARs on the subsynaptic membrane.After LTP, the increased Pr leads to the appearance of synaptic responses (after LTP, upper trace). In a synapse with low Pr (green) before LTP(lower trace), Pr can become closer to 1 as a result of LTP induction so that no failures appear after LTP (lower trace). (b) In postsynapticallysilent synapses, according to the latent AMPAR