大鼠海马可塑性改变对谷氨酸受体通道及其相关突触蛋白表达调控的研究

发布时间：2018-03-17 09:18

本文选题：突触可塑性　切入点：长时程增强　出处：《浙江大学》2006年博士论文　论文类型：学位论文

【摘要】：长时程增强(long-term potentiation,LTP)是一种由简单的高频刺激兴奋性输入端引起的突触强度的持续性增强,在大鼠海马,来自CA3区锥体细胞的Schaffer侧枝与CAl区锥体细胞树突形成突触,刺激schaffer侧枝使CAl区锥体细胞任何树突层受刺激均可诱出LTP。常用兴奋性突触后场电位(fEPSP)来判定突触传递是否强化以及是否出现。LTP作为神经科学研究当中衡量突触可塑性的一个主要的电生理指标,是研究得最为广泛的活性依赖的突触可塑性的细胞水平的模型,也是研究学习记忆的细胞水平的模型,它反映了突触可塑性变化中的神经电生理活动方面的改变。现在认为,药物依赖和学习记忆之间存在着某种共同的分子机制,即参与正常学习记忆的机制也可能参与了成瘾形成和发展。海马作为脑内主要的学习器官,其CAl区的神经元作为海马信息输出的最主要和最直接的贡献者,可以通过下托投射到其它包括奖励中枢和前额叶等许多脑区。在成瘾和戒断过程中,也可能发生了海马可塑性的改变。谷氨酸受体是海马内主要的兴奋性神经递质受体,兴奋性突触释放的谷氨酸主要与两种突触后离子型谷氨酸受体结合,它们是NMDA受体和AMPA受体。重组受体药理学和mRNA原位杂交研究提示NMDA受体可能有多种亚型,亚单位的不同组合方式和多样性是决定NMDA受体亚型多样性的重要基础。AMPA受体具有四个亚单位,为GluR1-4,在海马组织,AMPA受体的亚型主要为GluR1/2和GluR2/3,但在各核团,亚单位的分布也有差异。一般认为,NMDA受体在大多数通路中对诱导LTP是必需的,而AMPA受体则主要决定了LTP的表达和维持。神经元通过调节兴奋性突触后膜AMPA受体的数量和亚单位组成,可以改变兴奋性突触的活性和传递效能,因此,AMPA受体的膜转运也被认为是突触可塑性调节的重要环节。在突触上,NMDA受体以多蛋白复合物形式存在并起作用的,其中包括神经递质受体、细胞黏附蛋白、细胞骨架蛋白、支架蛋白、信号分子等,这种NMDA受体与多种信号通路在同一复合物中的共存是NMDA受体在突触可塑性、学习记忆中起重要作用的结构基础。受体在突触上
[Abstract]:Long term potentiation (LTP) is a sustained increase in synaptic intensity caused by simple high-frequency excitatory inputs. In the hippocampus of rats, the Schaffer collateral from the pyramidal cells in the CA3 region synapses with the dendrites of the CAl pyramidal cells. Stimulation of schaffer lateral branches can induce any dendritic layer of CAl pyramidal cells to be stimulated. Excitatory postsynaptic field potentials are commonly used to determine whether synaptic transmission is enhanced and whether. LTP occurs as a measure of synapse in neuroscience studies. A major electrophysiological indicator of plasticity, Is a model of the most widely studied active-dependent cellular level of synaptic plasticity, and a model of the cellular level of learning and memory, which reflects changes in neuroelectrophysiological activity in the changes in synaptic plasticity. There is a common molecular mechanism between drug dependence and learning and memory, that is, the mechanism involved in normal learning and memory may also be involved in the formation and development of addiction. The neurons in the CAl region, as the main and direct contributors to the output of hippocampal information, can be projected to many other brain regions, including the reward center and the prefrontal lobe. There may also be changes in hippocampal plasticity. Glutamate receptor is the main excitatory neurotransmitter receptor in hippocampus. Glutamate released by excitatory synapses mainly binds to two postsynaptic ionic glutamate receptors. They are NMDA receptor and AMPA receptor. Pharmacology of recombinant receptor and mRNA in situ hybridization indicate that NMDA receptor may have many subtypes. Different combinations and diversity of subunits are the important basis for determining the diversity of NMDA receptor subtypes. AMPA receptors have four subunits, GluR1-4. In hippocampal tissues, the subtypes of AMPA receptors are mainly GluR1/2 and GluR2 / 3, but in all nuclei. The distribution of subunits is also different. It is generally believed that NMDA receptors are necessary to induce LTP in most pathways. The expression and maintenance of LTP are mainly determined by AMPA receptors. Neurons can change the activity and transmission efficiency of excitatory synapses by regulating the number and subunit composition of AMPA receptors in excitatory postsynaptic membrane. Therefore, membrane transport of AMPA receptors is also considered to be an important link in synaptic plasticity regulation. NMDA receptors exist and function in the form of polyprotein complexes at synapses, including neurotransmitter receptors, cell adhesion proteins, cytoskeleton proteins. Scaffold proteins, signaling molecules, the coexistence of these NMDA receptors with multiple signaling pathways in the same complex is the structural basis of NMDA receptors that play an important role in synaptic plasticity, learning and memory.
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R33

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