NMDA依赖突触长时程增强及长时程抑制模型及仿真探究.docVIP

NMDA依赖突触长时程增强及长时程抑制模型及仿真探究 　 作者：董爱荣，谭小丹，苏永春，高天明， 邓亲恺 【关键词】 长时程增强 A model and simulation research of NMDAdepended bidirectional synaptic plasticit 　　【Astract】 AIM: To study the correlative mechanism between the induction of long term modification and the activity of different NMDA receptor subtypes. METHODS: Based on the analysis of dynamic properties of NMDA receptor subtypes, an amended mathematical model of postsynaptic calcium was proposed to describe the relationship between different NMDA receptor subtype activity and presynaptic stimulus frequency. Along with a biochemicalreaction networks model of the postsynaptic Ca2+depended signaling pathways, we developed a unified biophysical model about the hippocampal CA3CA1 synapses bidirectional plasticity. RESULTS: According to the inductive condition of longterm potentiation (LTP) and long term depression (LTD), our computer simulation mimicked the induction processes of NMDARdependent long term modification. CONCLUSION: It is elucidated that the calcium transients required for LTD may primarily come from the calcium inflow mediated by NR2B subtype channel of NMDA receptor and the induction of LTP may require the calcium inflow mediated by NR2B subtype channel. 　　【Keywords】 longterm potentiation; longterm depression; receptors, NmethylDAspartate; biophysical model 　　【摘要】 目的： 探究突触长时程增强和长时程抑制与NMDA受体亚型活性状态间的相关机制. 方法： 通过对NMDA受体亚型通道的动力学差异特性进行分析，提出一个修正的突触后钙信号模型来描述NMDA受体不同亚型的活性状态与突触前刺激频率的关系，并结合突触后钙依赖信号网络模型，建立了一个关于海马CA3CA1突触长时程增强和长时程抑制的生物物理模型. 结果： 根据LTP和LTD诱导条件，对NMDA依赖的突触长时程增强和长时程抑制的诱导和形成过程进行了仿真. 结论： 诱导LTD所需的钙暂态可能来源于NMDA通道的NR2B亚型的钙内流，而与LTP的诱导过程相对应的钙信号可能主要是通过该受体NR2A亚型通道的钙内流产生. 　　 　　【关键词】 长时程增强；长时程抑制；受体，N甲基D天冬氨酸；生物物理模型 　　0引言 　　海马神经元突触长时程增强（long term potentiation, LTP）和长时程压抑（long term depression, LTD）是突触长时程修饰的主要表现形式，是研究学习记忆过程的突触模型. NMDA受体的激活是海马CA3CA1突触LTP和LTD的诱导过程所必需的，同一种受体的激活如何能导致完全相反的突触强度修饰结果目前尚未明确［1］. 选择性地阻断含有NR2A或NR2B亚基的受体会导致该突触上LTP或LTD的诱导失败［2］. NMDA受体两种亚型通道所介导的不同钙暂态可能会导致突触后信号转导通路到达不同的稳态. 由于目前的实验条件很难对上述机制进行研究，我们意图通过模拟突触