NORADRENERGIC EXCITATION OF A SUBPOPULATION OF GABAergic CELLS IN THE BASOLATERAL AMYGDALA VIA BOTH ACTIVATION OF NONSELECTIVE CATIONIC CONDUCTANCE AND SUPPRESSION OF RESTING K+ CONDUCTANCE: A STUDY USING GLUTAMATE DECARBOXYLASE 67-GREEN FLUORESCENT PROTEIN KNOCK-IN MICE
NORADRENERGIC EXCITATION OF A SUBPOPULATION OF GABAergic CELLS IN THE BASOLATERAL AMYGDALA VIA BOTH ACTIVATION OF NONSELECTIVE CATIONIC CONDUCTANCE AND SUPPRESSION OF RESTING K+ CONDUCTANCE: A STUDY USING GLUTAMATE DECARBOXYLASE 67-GREEN FLUORESCENT PROTEIN KNOCK-IN MICE
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DOI：
10.1016/j.neuroscience.2008.09.029
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发表时间：
2008-12-10
期刊：
影响因子：
3.3
通讯作者：
Yanagawa, Y.
中科院分区：
文献类型：
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作者：
Kaneko, K.;Tamamaki, N.;Yanagawa, Y.
GABA能中间神经元在杏仁基底外侧核(BLA)神经元活动的调节中起重要作用。它们也被认为是脑干去甲肾上腺素能传入的主要靶点，参与了BLA相关记忆的增强。此外，行为应激已被证明削弱去甲肾上腺素促进GABA能传递。然而，去甲肾上腺素(NA)在BLA中的作用尚未在中到大型GABA能神经元和主细胞之间进行区分，其潜在机制仍有待阐明。谷氨酸脱羧酶67(GAD67)是GABA的生物合成酶，在GABA能神经元中特异表达。为了便于研究NA对活体制剂中GABA能神经元的影响，我们培育了GAD67绿色荧光蛋白(GFP)敲入小鼠，GFP在内源性GAD67基因启动子的控制下表达。在这里，我们发现GFP在这个GAD67-GFP敲入小鼠的BLA的GABA能神经元中特异性地表达。在体外全细胞膜片钳记录下，我们主要根据电生理特性确定了大脑白质内GABA能神经元的某一亚群。当通过电流注入去极化时，这些被称为A型神经元的神经元以相对较低的频率产生动作电位。我们发现NA通过α(1)-肾上腺素受体直接兴奋A型细胞，而对其他类型神经元的影响可以忽略不计。这种兴奋性涉及两种离子机制：激活非选择性阳离子电导和抑制静息K+电导。NA还可增加BLA主细胞自发IPSCs的频率。提示A型细胞的NA依赖的兴奋在一定时间内减弱了BLA的输出。(C)2008年IBRO。爱思唯尔有限公司出版。保留所有权利。
GABAergic interneurons play central roles in the regulation of neuronal activity in the basolateral nucleus of the amygdala (BLA). They are also suggested to be the principal targets of the brainstem noradrenergic afferents which are involved in the enhancement of the BLA-related memory. In addition, behavioral stress has been shown to impair noradrenergic facilitation of GABAergic transmission. However, the noradrenaline (NA) effects in the BLA have not been differentiated among medium- to large-sized GABAergic neurons and principal cells, and remain to be elucidated in terms of their underlying mechanisms. Glutamate decarboxylase 67 (GAD67) is a biosynthetic enzyme of GABA and is specifically expressed in GABAergic neurons. To facilitate the study of the NA effects on GABAergic neurons in live preparations, we generated GAD67-green fluorescent protein (GFP) knock-in mice, in which GFP was expressed under the control of an endogenous GAD67 gene promoter. Here, we show that GFP was specifically expressed in GABAergic neurons in the BLA of this GAD67-GFP knock-in mouse. Under whole-cell patch-clamp recordings in vitro, we identified a certain subpopulation of GABAergic neurons in the BLA chiefly on the basis of the electrophysiological properties. When depolarized by a current injection, these neurons, which are referred to as type A, generated action potentials at relatively low frequency. We found that NA directly excited type-A cells via alpha(1)-adrenoceptors, whereas its effects on the other types of neurons were negligible. Two ionic mechanisms were involved in this excitability: the activation of nonselective cationic conductance and the suppression of the resting K+ conductance. NA also increased the frequency of spontaneous IPSCs in the principal cells of the BLA. It is suggested that the NA-dependent excitation of type-A cells attenuates the BLA output for a certain period. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.