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成年小鼠前脑NMDA受体参与神经元的动作电位发放

王过渡, 卓敏

多伦多大学医学院生理系,多伦多大学痛觉研究中心,多伦多,安大略省M5S1A8

摘要

谷氨酸是中枢神经系统主要的快速兴奋性递质。AMPA受体和海人藻酸受体主要参与突触传递，而NMDA受体主要参与突触可塑性。基因操作的方法增强NMDA受体的功能，可以增强动物在正常生理状态下的学习能力，及在组织损伤情况下的反应敏感性。NMDA受体参与生理功能的主要机制是长时程增强（long--term potentiation，LTP）。作者的研究表明，NMDA受体不仅参与刺激前扣带皮层的第五层细胞或刺激白质诱导的突触反应，而且参与在胞体施加去极化跃阶电流诱导的动作电位的发放。钙--钙调蛋白敏感的腺苷酸环化酶1（adenylyl cyclase 1，AC1）和cAMP信号通路可能介导了这些反应。由于扣带皮层神经元在伤害性刺激和痛中发挥重要作用，作者的结果为前脑NMDA受体参与突触传递和动作电位发放，以及与前脑相关的行为，如感受伤害性刺激和痛，提供了一个新的机制。

关键词： 前扣带皮层; NMDA受体; 腺苷酸环化酶; 动作电位; cAMP; 小鼠

Forebrain NMDA receptors contribute to neuronal spike responses in adult mice

Wang Guodu, Zhuo Min

Department of Physiology, University of Toronto Center for the Study of Pain, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S1AS

Abstract

Glutamate is the major fast excitatory transmitter in the central nervous system. While normal synaptic transmission is mediated by #alpha#-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid （AMPA） and kainate receptors, N-methyl-D-aspartate （NMDA） receptors are thought to selectively contribute to plasticity. Genetically enhancing NMDA receptor functions enhances animal behavior in normal physiological learning and enhances their sensitivity in the case of tissue injury. One major mechanism for NMDA receptors is synaptic long-term potentiation （LTP）. Here we present evidence that NMDA receptors not only contribute to normal synaptic responses induced by stimulation of local layer V or white matters, but also contribute to generation of action potentials induced by a depolarizing step applied to the soma. Calcium-calmodulin sensitive adenylyl cyclase 1 and cAMP signal pathways likely mediate these effects. Considering the importance of cingulate neurons in nociception and pain, our results provide a new mechanism for NMDA receptor contributing to neuronal synaptic transmission, spiking properties in forebrains, and possible forebrain-related behavioral nociceptive responses and pain.

Key words: anterior cingulate cortex;NMDA receptor;Adenylyl cyclase;Action potential;cAMP;Mice

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引用本文：

王过渡, 卓敏. 成年小鼠前脑NMDA受体参与神经元的动作电位发放[J]. 生理学报 2006; 58 (6): .

Wang Guodu, Zhuo Min. Forebrain NMDA receptors contribute to neuronal spike responses in adult mice. Acta Physiol Sin 2006; 58 (6): (in Chinese with English abstract).