大鼠海马CA1区神经元高级可塑性（Metaplasticity）的研究
文献类型：学位论文
| 作者 | 张继川 |
| 学位类别 | 博士 |
| 答辩日期 | 2005-01 |
| 授予单位 | 中国科学院研究生院 |
| 授予地点 | 北京 |
| 导师 | 徐林 |
| 关键词 | 微小兴奋性突触后膜电流（mEPSC） 辣椒素 长时程抑制（LTD） 长时程增强（LTP） 海马 高级可塑性（metaplasticity） 突触可塑性 |
| 中文摘要 | 经验（experience）或突触活动依赖的突触信息传递效能的增强（LTP）或抑制（LTD）被称为突触可塑性（synaPticplasticity），是公认的学习和记忆的细胞分子学基础。突触可塑性的方向是突触信息传递效能的增强或降低；突触可塑性的程度是突触信息传递的效能增加量或降低量。突触活动历史可影响随后突触可塑性的方向或程度。这种突触可塑性的可塑性被称为高级可塑性（MetaP1asticity）。最明显的高级可塑性现象是发生在突触效能没有改变的情况下。经验或者突触活动可以同时诱导出突触可塑性和高级可塑性。除非知道突触活动的历史，否则很难预测突触可塑性的大小和方向。高级可塑性简单地讲就是过去的神经信息留下痕迹会对神经信息的加工处理产生持续性影响。目前高级可塑性的机理并不完全清楚。采用全细胞电压钳记录方法，在3周龄wistar大鼠海马脑片中，同时记录schaffer侧枝纤维一以1处兴奋性突触后膜电流（evokedEPsC）和自发性微小兴奋性突触后膜"电流（mEPSC）。结果显示，mEPSC和低频刺激诱导的长时程抑制（Long一TermDePre55ion，LTD）之间呈负相关，mEPsc的频率或幅值越小，诱导出的LTD幅度越大；应激和低钙溶液处理在降低记PsC的频率和幅值的同时并没有明显改变随后LTD的诱导幅，但是这两者负相关性依然存。相关系数在应激条件下有增加，在低钙溶液中有降低。以上结果提示，mPEsc的频率或幅值可能指示了过去的突触活动或经验产牛的高幼可朔件＿田、冲稀恻了喃层的，：。、云导的幅度。C鹉子妙触可黔和高级可黔中起着关键作。作为一种非选择性阳离子通道，van11101drec即tortyPel（VR1或TRPVI）在脑区中广泛表达，尤其在海马高表达。内源性配体可以激活该受体通道。但目前并不清楚vRI在海马突触可塑性当中的作用。我们发现VRI激动剂辣椒素不影响脑片中海马以1区基础突触传递，但是它阻断低频诱导（LFS，3Hz）的LTD，增强高频诱导（HFs，20OHz）的长时程增强（Long一TerlnPotetiantion，LTP）。也就是vRI激活改变了突触可塑性的方向，是一种经典的高级可塑性现象。正常情况下50Hz不能诱导出LTP，而加入辣椒素后易化了LTP的诱导。因此LTP诱导的闽值降低。辣椒素激动剂对突触可塑性或高级可塑性的效应不依赖协。A受体而依赖于H型钙调蛋白激酶（CaMKII）的调控。因为场。A受体电流和它的电流一电压曲线不受此激动剂影响，但CaMKII抑制剂KN-93或者VRI拮抗剂capsazepine却阻断了辣椒素的这种效应。这些发现，显示VRI可以调控海马以1区的高级突触可塑性，可能参与某些类型的学习和记忆。 |
| 英文摘要 | Synpatic plasticity is termed as the change of synaptic efficacy, which putatively underlies learning and memory. The direction or degree for synaptic plasticity can be persistently changed by prior synaptic or cellular activity. This plasticity of synaptic plasticity is termed metaplasticity. The mechanism of metaplasticity is not fully understood, especially when the synaptic strength is changed by synaptic activity. Metaplasticity and synaptic plasticity can be induced simultaneously by the same synaptic activity. Therefore, in the synaptic plasticity studies in vitro or in anaesthetized animals in vivo, one hardly predicts the magnitude of LTP or LTD unless the previous activity history of the synapses is known. Here, we have recorded simultaneously the excitatory postsynaptic currents (EPSC) and miniature EPSC (mEPSC) in the Schaffer-CAl synapses in 3-week old Wistar rat slice using whole-cell voltage-clamp techniques. We find an inverse relationship between mEPSC and long-term depression (LTD) induction, in which lower frequency or smaller amplitude of mEPSC is significantly correlated to larger magnitude of LTD. Exposure to behavioral stress immediately before slice preparation or low calcium concentration in bath solution is able to decrease the frequency and amplitude of mEPSC. Under these conditions, the magnitude of LTD does not become significantly larger. However, the frequency or amplitude of mEPSC still inversely correlates to the magnitude of LTD. The correlation coefficient is increased in the stressed condition, but it is decreased by the low calcium bath solution. These findings suggest that the frequency or amplitude of mEPSC may indicate the occurrence of metaplasticity by previous synaptic activity or experience to predict the degree for subsequent LTD induction. Calcium plays a crucial role in synaptic plasticity and metaplasticity. Vanilloid receptor type 1 (VRl, also known as TRPVl), a non-selective cation channel, is expressed widely in brain regions including the hippocampus. Endougenious ligands can activate VRl. It is unclear whether VRl is involved in hippocampal synaptic plasticity. Here we report that the VRl,agonist capsaicin does not affect the basal excitatory postsynaptic currents (EPSC) in the hippocampal CAl area in young rat slice. But it blocks long-term depression (LTD) induction by low frequency stimulation (LFS, 3Hz) and enhances long-term potentiation (LTP) induction by high frequency stimulation (HFS, 200Hz). VRl activation can change the direction of synaptic plasticity, a typical metaplasticity phemomena. Moreover, capsaicin enables LTP induction by HFS at 50Hz that failed to induce LTP in control condition. These are not due to the direct actions of capsaicin on NMDA receptor since it does not affect the NMDA receptor mediated-currents or I-V curve of the currents. Either the CaMKII inhibitor KN-93 or the VRl antagonist capsazepine blocks the actions of capsaicin on the induction of LTP and LTD. These findings suggest that VR1 is able to modulate metaplasticity in the CAl area of the hippocampus, potentially regulating certain types of learning and memory. |
| 语种 | 中文 |
| 公开日期 | 2010-10-15 |
| 源URL | [http://159.226.149.42:8088/handle/152453/6170]  |
| 专题 | 昆明动物研究所_学习记忆的分子神经机制 |
| 推荐引用方式 GB/T 7714 | 张继川. 大鼠海马CA1区神经元高级可塑性（Metaplasticity）的研究[D]. 北京. 中国科学院研究生院. 2005. |
入库方式： OAI收割
来源：昆明动物研究所
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