Novel subunit-specific tonic GABA currents and differential effects of ethanol in the central amygdala of CRF receptor-1 reporter mice.
Novel subunit-specific tonic GABA currents and differential effects of ethanol in the central amygdala of CRF receptor-1 reporter mice.
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DOI：
10.1523/jneurosci.2490-12.2013
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发表时间：
2013-02-20
期刊：
影响因子：
--
通讯作者：
Roberto M
中科院分区：
文献类型：
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作者：
Herman MA;Contet C;Justice NJ;Vale W;Roberto M
杏仁中央核(CEA)是酒精等滥用药物强化效应的重要整合部位。CEA中促肾上腺皮质激素释放因子1(CRF1)受体的激活在酒精依赖的形成中起着关键作用，但这些神经元的特征仍不明确。利用CRF1：GFP报告小鼠和电生理/免疫组织化学相结合的方法，我们发现CRF1神经元表现出GABA 1受体亚单位介导的紧张性电导，该电导由动作电位依赖的α释放驱动。相反，未标记的CEA神经元显示了δ亚单位介导的紧张性电导，该电导可被乙醇增强。乙醇增加CRF1神经元的放电，减少未标记的CEA神经元的放电。逆行追踪研究表明，CEA、CRF1神经元投射到终纹床核。综上所述，这些数据展示了特定亚基的紧张性信号，并提供了对乙醇对CEA微电路的具体影响的机械性洞察。
The central nucleus of the amygdala (CeA) is an important integrative site for the reinforcing effects of drugs of abuse, such as ethanol. Activation of corticotropin-releasing factor type 1 (CRF1) receptors in the CeA plays a critical role in the development of ethanol dependence, but these neurons remain uncharacterized. Using CRF1:GFP reporter mice and a combined electrophysiological/immunohistochemical approach, we found that CRF1 neurons exhibit an α1 GABAA receptor subunit-mediated tonic conductance that is driven by action potential-dependent GABA release. In contrast, unlabeled CeA neurons displayed a δ subunit-mediated tonic conductance that is enhanced by ethanol. Ethanol increased the firing discharge of CRF1 neurons and decreased the firing discharge of unlabeled CeA neurons. Retrograde tracing studies indicate that CeA CRF1 neurons project into the bed nucleus of the stria terminalis. Taken together, these data demonstrate subunit-specific tonic signaling and provide mechanistic insight into the specific effects of ethanol on CeA microcircuitry.