本文選題：突觸可塑性　切入點：長時程增強　出處：《浙江大學》2006年博士論文　論文類型：學位論文

【摘要】：長時程增強(long-term potentiation,LTP)是一種由簡單的高頻刺激興奮性輸入端引起的突觸強度的持續(xù)性增強,在大鼠海馬,來自CA3區(qū)錐體細胞的Schaffer側枝與CAl區(qū)錐體細胞樹突形成突觸,刺激schaffer側枝使CAl區(qū)錐體細胞任何樹突層受刺激均可誘出LTP。常用興奮性突觸后場電位(fEPSP)來判定突觸傳遞是否強化以及是否出現(xiàn)。LTP作為神經(jīng)科學研究當中衡量突觸可塑性的一個主要的電生理指標,是研究得最為廣泛的活性依賴的突觸可塑性的細胞水平的模型,也是研究學習記憶的細胞水平的模型,它反映了突觸可塑性變化中的神經(jīng)電生理活動方面的改變。現(xiàn)在認為,藥物依賴和學習記憶之間存在著某種共同的分子機制,即參與正常學習記憶的機制也可能參與了成癮形成和發(fā)展。海馬作為腦內(nèi)主要的學習器官,其CAl區(qū)的神經(jīng)元作為海馬信息輸出的最主要和最直接的貢獻者,可以通過下托投射到其它包括獎勵中樞和前額葉等許多腦區(qū)。在成癮和戒斷過程中,也可能發(fā)生了海馬可塑性的改變。 谷氨酸受體是海馬內(nèi)主要的興奮性神經(jīng)遞質(zhì)受體,興奮性突觸釋放的谷氨酸主要與兩種突觸后離子型谷氨酸受體結合,它們是NMDA受體和AMPA受體。重組受體藥理學和mRNA原位雜交研究提示NMDA受體可能有多種亞型,亞單位的不同組合方式和多樣性是決定NMDA受體亞型多樣性的重要基礎。AMPA受體具有四個亞單位,為GluR1-4,在海馬組織,AMPA受體的亞型主要為GluR1/2和GluR2/3,但在各核團,亞單位的分布也有差異。一般認為,NMDA受體在大多數(shù)通路中對誘導LTP是必需的,而AMPA受體則主要決定了LTP的表達和維持。神經(jīng)元通過調(diào)節(jié)興奮性突觸后膜AMPA受體的數(shù)量和亞單位組成,可以改變興奮性突觸的活性和傳遞效能,因此,AMPA受體的膜轉(zhuǎn)運也被認為是突觸可塑性調(diào)節(jié)的重要環(huán)節(jié)。在突觸上,NMDA受體以多蛋白復合物形式存在并起作用的,其中包括神經(jīng)遞質(zhì)受體、細胞黏附蛋白、細胞骨架蛋白、支架蛋白、信號分子等,這種NMDA受體與多種信號通路在同一復合物中的共存是NMDA受體在突觸可塑性、學習記憶中起重要作用的結構基礎。受體在突觸上
[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.
【學位授予單位】：浙江大學
【學位級別】：博士
【學位授予年份】：2006
【分類號】：R33

【引證文獻】

相關碩士學位論文 前2條

1 王宗青;mGluR_1在單眼形覺剝奪弱視大鼠視皮質(zhì)17區(qū)的表達及神經(jīng)元超微結構觀察[D];新鄉(xiāng)醫(yī)學院;2007年

2 沈亞君;兩種芋螺毒素類似物抑制嗎啡誘導小鼠條件性位置偏愛及nNOS表達的研究[D];浙江大學;2012年

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本文編號：1624095