Impairment of suckling response, trigeminal neuronal pattern formation, and hippocampal LTD in NMDA receptor epsilon 2 subunit mutant mice

Impairment of suckling response, trigeminal neuronal pattern formation, and hippocampal LTD in NMDA receptor epsilon 2 subunit mutant mice
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DOI:
10.1016/s0896-6273(00)80051-3
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发表时间:
1996-02-01
期刊:
影响因子:
16.2
通讯作者:
Mishina, M
Mishina, M
中科院分区:
医学1区
文献类型:
--
作者:
Kutsuwada, T;Sakimura, K;Mishina, M

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多个NMDA受体亚基是NMDA受体通道多样性的主要决定因素。基于它们在体外的功能特性和分布,我们提出了突触可塑性的作用,在突触可塑性中发挥作用的EST1和EST2亚基。为了研究NMDA受体通道多样性的生理学意义,我们产生了在NMDA受体2亚基中有缺陷的突变小鼠。这些小鼠没有表现出吸吮反应,出生后不久死亡,但可以通过手喂养存活。该突变阻碍了胡须相关的神经元barriotette结构的形成和初级感觉传入终末在脑干三叉神经核的聚集。在突变小鼠的海马中,突触NMDA反应和长时程抑郁被消除。这些结果表明,在神经元模式的形成和突触可塑性的α 2亚基起着至关重要的作用。
Multiple epsilon subunits are major determinants of the NMDA receptor channel diversity. Based on their functional properties in vitro and distributions, we have proposed that the epsilon 1 and epsilon 2 subunits play a role in synaptic plasticity. To investigate the physiological significance of the NMDA receptor channel diversity, we generated mutant mice defective in the epsilon 2 subunit. These mice showed no suckling response and died shortly after birth but could survive by hand feeding.The mutation hindered the formation of the whisker-related neuronal barrelette structure and the clustering of primary sensory afferent terminals in the brain-stem trigeminal nucleus. In the hippocampus of the mutant mice, synaptic NMDA responses and long-term depression were abolished. These results suggest that the epsilon 2 subunit plays an essential role in both neuronal pattern formation and synaptic plasticity.