乙醇对基底外侧杏仁核神经元放电的抑制作用是由γ-氨基丁酸 A 型介导的紧张性电流介导的。
The ethanol inhibition of basolateral amygdala neuron spiking is mediated by a γ-aminobutyric acid type A-mediated tonic current.
机构信息
Department of Neuroscience, Medical University of South Carolina, Charleston, South Carolina, USA.
Addiction Sciences Division, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina, USA.
出版信息
Alcohol Clin Exp Res. 2022 Sep;46(9):1665-1676. doi: 10.1111/acer.14918. Epub 2022 Aug 11.
BACKGROUND
The basolateral nucleus of the amygdala (BLA) plays an important role in the development of fear and anxiety-related behaviors. The BLA receives inputs from all sensory stimuli. After processing those stimuli, BLA neurons signal neurons within the central amygdala and other brain regions, including the ventral and dorsal striatum and frontal cortex. Studies suggest that the BLA is involved in drug dependence and in the reinforcing actions of ethanol. For example, acute exposure to ethanol reduces anxiety, while withdrawal from chronic ethanol exposure alters BLA synaptic transmission, which increases anxiety, a common underlying cause of relapse. Exposure to and withdrawal from chronic alcohol also disrupts many brain areas that connect with the BLA. Despite these important findings, the acute actions of alcohol on the intrinsic excitability of BLA neurons have not been fully characterized.
METHODS
Brain slices containing the BLA were prepared from adult C57BL/6J male mice. Whole-cell and sharp electrode electrophysiological recordings were performed to characterize the effects of acute ethanol on BLA neuronal and astrocyte function, respectively.
RESULTS
Ethanol inhibited action potential (AP) firing of BLA neurons but had no effect on BLA astrocyte resting membrane potential. The ethanol-induced inhibition of firing was concentration-dependent (11 to 66 mM) and accompanied by a reduction in the input resistance and an increase in the rheobase of BLA neurons. The inhibitory effect of ethanol was suppressed by picrotoxin, which blocks both γ-aminobutyric acid type A (GABA ) and glycine receptors, but not by the selective glycine receptor antagonist strychnine, which suggests an involvement of GABA receptors. Ethanol did not affect spontaneous inhibitory postsynaptic currents suggesting that the inhibition of BLA neuronal excitability by ethanol was not due to an increase in GABA -mediated synaptic transmission. However, acute ethanol enhanced the amplitude of the holding current of BLA neurons, an effect that was prevented by picrotoxin, which by itself reduced the holding current.
CONCLUSIONS
These results suggest that BLA neurons express a GABA-mediated tonic current that is enhanced by acute ethanol, which leads to reduced excitability of BLA neurons.
背景
杏仁基底外侧核（BLA）在恐惧和焦虑相关行为的发展中起着重要作用。BLA 接收来自所有感觉刺激的输入。在处理这些刺激后，BLA 神经元向中杏仁核和其他大脑区域（包括腹侧和背侧纹状体和额叶皮层）的神经元发出信号。研究表明，BLA 参与了药物依赖和乙醇的强化作用。例如，急性暴露于乙醇会降低焦虑，而从慢性乙醇暴露中戒断会改变 BLA 突触传递，从而增加焦虑，这是复发的常见潜在原因。暴露于慢性酒精并从中戒断也会破坏与 BLA 相连的许多大脑区域。尽管有这些重要的发现，但乙醇对 BLA 神经元内在兴奋性的急性作用尚未得到充分描述。
方法
从成年 C57BL/6J 雄性小鼠中制备包含 BLA 的脑片。进行全细胞和尖锐电极电生理记录，分别表征急性乙醇对 BLA 神经元和星形胶质细胞功能的影响。
结果
乙醇抑制 BLA 神经元动作电位（AP）放电，但对 BLA 星形胶质细胞静息膜电位没有影响。乙醇诱导的放电抑制作用呈浓度依赖性（11 至 66mM），并伴有 BLA 神经元输入电阻降低和基强度增加。乙醇的抑制作用被 picrotoxin 抑制，picrotoxin 阻断 GABA 型 A（GABA A）和甘氨酸受体，而不是选择性甘氨酸受体拮抗剂士的宁，这表明 GABA 受体的参与。乙醇不影响自发性抑制性突触后电流，这表明乙醇对 BLA 神经元兴奋性的抑制不是由于 GABA 介导的突触传递增加所致。然而，急性乙醇增强了 BLA 神经元保持电流的幅度，这种作用被 picrotoxin 阻止，picrotoxin 本身降低了保持电流。
结论
这些结果表明，BLA 神经元表达一种由 GABA 介导的紧张性电流，急性乙醇增强了这种电流，导致 BLA 神经元兴奋性降低。
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