GABA(B) receptor activation inhibits neuronal excitability and spatial learning in the entorhinal cortex by activating TREK-2 K+ channels.

GABA(B) receptor activation inhibits neuronal excitability and spatial learning in the entorhinal cortex by activating TREK-2 K+ channels.
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DOI:
10.1016/j.neuron.2009.06.022
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发表时间:
2009-07-30
期刊:
影响因子:
16.2
通讯作者:
Lei, Saobo
Lei, Saobo
中科院分区:
医学1区
文献类型:
--
作者:
Deng, Pan-Yue;Xiao, Zhaoyang;Yang, Chuanxiu;Rojanathammanee, Lalida;Grisanti, Laurel;Watt, John;Geiger, Jonathan D.;Liu, Rugao;Porter, James E.;Lei, Saobo

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内嗅皮层(EC)被认为是通往海马体的门户,因此对学习和记忆是必不可少的。虽然EC表达高密度的GABAB受体,但这些受体在该区域的功能仍未被探索。在这里,我们研究了GABAB受体激活对EC和空间学习中神经元兴奋性的影响。应用GABAB受体激动剂巴氯芬可显著抑制EC神经元的兴奋性。GABAB受体介导的EC抑制是通过激活Trek-2介导的,Trek-2是一种双孔结构域K+通道,需要抑制性G蛋白和蛋白激酶A途径的作用。通过Morris水迷宫评估,EC中神经元兴奋性的抑制是GABAB受体介导的空间学习抑制的基础。我们的研究表明,GABAB受体通过调节EC中神经元的兴奋性,对空间学习起着严格的控制作用。
The entorhinal cortex (EC) is regarded as the gateway to the hippocampus and thus is essential for learning and memory. Whereas the EC expresses a high density of GABAB receptors, the functions of these receptors in this region remain unexplored. Here we examined the effects of GABAB receptor activation on neuronal excitability in the EC and spatial learning. Application of baclofen, a specific GABAB receptor agonist, inhibited significantly neuronal excitability in the EC. GABAB receptor-mediated inhibition in the EC was mediated via activating TREK-2, a type of two-pore domain K+ channels and required the functions of inhibitory G proteins and protein kinase A pathway. Depression of neuronal excitability in the EC underlies GABAB receptor-mediated inhibition of spatial learning as assessed by Morris water maze. Our study indicates that GABAB receptors exert a tight control over spatial learning by modulating neuronal excitability in the EC.
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