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1、神经元的电活动与突触传递,医学神经生物学国家重点实验室,来 滨,什么是神经元电活动？如何形成的？ 什么是突触？ 为什么突触传递在神经科学研究中如此重要？,脑：信息的传递和处理,神经元电活动的基础 离子通道,离子通道的一般特征,物理特征 离子选择性 通道激活模式 开放和关闭,物理特性,胞外,胞内,胞外,跨膜 孔道 膜内和膜外侧扩大形成腔 膜内段缩窄有门控结构,通道的离子选择性,特殊：某些通道特异性小，甚至允许小的有机物质通过。,阴离子通道的特异性较小，它们之所以称为 Cl-通道是因为Cl-是生物溶液的主要阴离子,通道的选择性是相对的，例如钠通道不但对钠离子通透，对 铵（NH4+）也通透；甚至对钾
2、离子也稍有通透。,胞外,胞内,60mv,通道离子选择性和电压感受的机制,电压激活模式 牵张激活模式 配体激活通道,通道激活模式,注意,以上分类并非绝对的； 例如钙激活钾通道 也对电压变化敏感， 有些电压激活通道 也对细胞内配体敏感！,离子通道的分类,选择性阳离子通道,非选择性阳离子通道,阴离子通道,跨膜转运系统,钠钾泵 钙泵 钠钙泵,氯离子通道,门控离子通道,化学门控离子通道,非门控离子通道,电压门控离子通道,离子通道的分类（门控方式）,跨膜转运系统,钠钾泵 钙泵 钠钙泵 ATP ATP Na+化学 梯度 K+:Na+ Ca2+ Na+:Ca2+ 2:3 3:1 生电性 生电性 生电性,轴突的
3、终端为轴突末梢，它终止于另一神经元或效应器，与它们形成突触。,轴突末梢 (axon terminals),每个神经元大约会有1万个突触,突触（synapse） 定义：一个神经元与另一个神经元相接触的部位叫做突触。突触是神经元之间在功能上发生联系的部位，也是信息传递的关键部位。,电突触,1 m,化学突触,化学突触的结构,突触传递相关受体,突触后电流: 突触前释放神经递质激活突触后膜相应受体引起的突触后膜的电流变化。去极化的电流变化称作兴奋性突出后电流，超极化的电流变化称作抑制性突触后电流。,突触后电位参与动作电位的形成,轴突动作电位,突触前囊泡释放,突触后膜受体激活,突触后电位,突触后膜受体和离
4、子通道分布和类型,其他不同突触活动,突触前膜离子通道分布和类型,突触前膜离子通道分布和类型 突触囊泡施放相关蛋白的功能,轴突局部环境对信息的影响和调控,轴突局部离子通道分布，类型,轴突局部离子通道分布，类型对信息传递的影响,NATURE| Vol 465|24 June 2010,NATURE| Vol 465|24 June 2010,膜电位超极化,局部突触活动对信息传递的影响,突触前膜离子通道分布和类型 以及突触囊泡施放相关蛋白的功能,Neuron 59, September 25, 2008,突触囊泡释放机制,mEPPs provide evidence that synaptic tr
5、ansmission is quantal (vesicular),突触后膜受体和离子通道分布和类型,Activity-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 den
6、sity (PSD) are internalized during LTP, requiring Ca2+ 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 Ca
7、2+ influx and protein phosphatase-2B (PP2B) activation (3). Glial glutamate transporters (GLT) also influence Kv2.1 dephosphorylation through their regulation of extrasynaptic NMDARKv2.1 channel coupling,Trends in Neurosciences Vol.33 No.7,动作电位在突触后神经元产生： EPSP在轴突的始段达到-52mV左右时，就可以引发动作电位。 始段爆发的动作电位向两个方
8、向扩布。 逆向扩布的动作电位将刷新神经元胞体的状态。,信息流,突触传递的逆向调节,信息流,Neuron 63, July 30, 2009,电突触,电突触的结构,电突触的分布和功能,Electrical synapse： nervous system，cardiac muscle,smooth muscle and liver。 电镜发现：哺乳类动物的大脑皮层感觉区星状cell,小脑皮层蓝细胞与星状细胞，视网膜水平细胞与双极细胞，嗅球的僧帽细胞以及神经胶质细胞均存在着电突触。 Function： in excitable cell:电突触双向快速传递，传递空间减少，则传递更有效，突触灵活性增加
9、，有利于机能相似的细胞进行同步活动。低电阻通路还可调节细胞间小分子量物质的转移。而细胞间的化学突触传递易于受到代谢障碍的明显影响，而电突触具有较大的耐受力。 in nonexcitable cell:它是和生长代谢的控制，胚胎的发育及分化等现象有关。它可运输某些代谢产物和营养物质。,电突触突触电位,两个膜紧密接触，离子通道相通,离子,胶质细胞对突触传递的影响,胶质细胞：脑中数量最多的细胞,神经元：目前认为是脑功能实现的主体,血管，结缔组织等：营养保护作用,胶质细胞的数量是神经元的十倍！,人脑中有约1000亿个神经元,似乎胶质细胞更为重要但是对于大脑的独特功能来说，神经元更为重要！ 原因：神经元
10、能够感知环境的变化并将信息传递给其它神经元指令机体作出反应。,胶质细胞其隔离、支持、保护、营养神经元的作用,但是越来越多的研究正使我们对胶质细胞的功能发生全新的改变。 有人研究爱因斯坦的大脑后发现其大脑的胶质细胞量显著高于普通人70！ 新的研究已经证明胶质细胞在神经元信息处理过程中有着有着重要作用。,Mechanisms regulating glial glutamate transporter levels. Astrocytes play an active role in the removal of neurotransmitters from the synapse via tra
11、nsport 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 neuronastrocyte communication limit
12、s glutamate transporter abundance, thereby contributing to modulation of synaptic plasticity.,The tripartite synapse. When neurotransmitters are released from the presynaptic neuron (1), astrocytic metabotropic glutamate receptors (mGluRs) are activated leading to a rise in Ca2+ ions in the astrocyt
13、e (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 postsynaptically on NMDARs thereby enhancing excita
14、bility 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 can regulate synaptic plasticity (4). Astro
15、cytic 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.,Interplay between astrocytes, neurons and the vasculature. (a) Astrocytes are connected via gap j
16、unctions 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. Astrocytes, either as individuals (as shown here) or as part
17、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.,沉默突触（Silence synapse）,沉默是金！Silence is gold！,whose existence has been recognized long ago (Mendell 198
18、4）,普遍认为，在神经元的发育早期，大多数突触后膜上只含NMDA受体而不含AMPA受体。随着神经系统的发育成熟，AMPA受体的转运上膜后才有大量功能性突触的产生。研究者也习惯的把只含NMDA受体的突触定义为沉默突触（silent synapse）。,概念,暂时没有信息传递功能的突触,Involvement of presynaptically or postsynaptically silent synapses in LTP maintenance. Presynaptic terminals contacting postsynaptic spines are schematically
19、represented before and after LTP. (a) In presynaptically silent synapses (yellow) with low release probability (Pr) no responses can be detected before LTP (upper trace) in spite the expression of functional AMPARs and NMDARs on the subsynaptic membrane. After LTP, the increased Pr leads to the appe
20、arance 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 postsynaptically silent synapses, according to the latent AMPARs hypothe
21、sis (Malenka and Nicoll, 1999) before LTP, some synapses containing only NMDARs (yellow) are not active at resting membrane potential (upper trace). Insertion of new AMPARs makes the synapse conductive (after LTP, upper trace). Potentiation following insertion of new AMPARs may occur also in synapse
22、s previously effective (green). The hypothesis explains the decrease in failure rate in previously effective synapses suggesting fast addition of AMPAR clusters also in cases when the number of apparently silent synapses is small as in the hippocampus of adult animals.,沉默突触的机制假说,突触前沉默的机制,突触后沉默的机制,突触后,AMPA,NMDA,Glu,Glu,Mg2+,膜去极化,AMPA受体的作用机制,沉默突触的功能是什么？,作为脑学习记忆功能的一种能力储备,谢谢大家,