Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Center for Animal MRI, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Alcohol. 2024 May;116:53-64. doi: 10.1016/j.alcohol.2024.02.004. Epub 2024 Feb 27.
The central amygdala (CeA) and bed nucleus of the stria terminalis (BNST) are reciprocally connected nodes of the extended amygdala thought to play an important role in alcohol consumption. Studies of immediate-early genes indicate that BNST and CeA are acutely activated following alcohol drinking and may signal alcohol reward in nondependent drinkers, while stress signaling in the extended amygdala following chronic alcohol exposure drives increased drinking via negative reinforcement. However, the temporal dynamics of neuronal activation in these regions during drinking behavior are poorly understood. In this study, we used fiber photometry and the genetically encoded calcium sensor GCaMP6s to assess acute changes in neuronal activity during alcohol consumption in BNST and CeA before and after a chronic drinking paradigm. Activity was examined in the pan-neuronal population and separately in dynorphinergic neurons. BNST and CeA showed increased pan-neuronal activity during acute consumption of alcohol and other fluid tastants of positive and negative valence, as well as highly palatable chow. Responses were greatest during initial consummatory bouts and decreased in amplitude with repeated consumption of the same tastant, suggesting modulation by stimulus novelty. Dynorphin neurons showed similar consumption-associated calcium increases in both regions. Following three weeks of continuous alcohol access (CA), calcium increases in dynorphin neurons during drinking were maintained, but pan-neuronal activity and BNST-CeA coherence were altered in a sex-specific manner. These results indicate that BNST and CeA, and dynorphin neurons specifically, are engaged during drinking behavior, and activity dynamics are influenced by stimulus novelty and chronic alcohol.
中杏仁核（CeA）和终纹床核（BNST）是相互连接的扩展杏仁核节点，被认为在酒精消费中发挥重要作用。即时早期基因的研究表明，BNST 和 CeA 在饮酒后会被急性激活，并且可能在非依赖饮酒者中发出酒精奖励信号，而慢性酒精暴露后在扩展杏仁核中的应激信号通过负强化驱动饮酒增加。然而，这些区域在饮酒行为期间神经元激活的时间动态知之甚少。在这项研究中，我们使用光纤光度法和基因编码钙传感器 GCaMP6s 来评估 BNST 和 CeA 在慢性饮酒范式前后在酒精消费期间神经元活动的急性变化。在整个神经元群体中以及在 dynorphinergic 神经元中分别检查了活性。BNST 和 CeA 在急性酒精和其他具有正价和负价的液体味觉以及极美味的饲料消耗期间表现出整个神经元活动的增加。反应在最初的消耗回合中最大，并随着相同味觉的重复消耗而降低幅度，表明受刺激新颖性的调节。两种区域的 dynorphin 神经元均显示出类似的与消耗相关的钙增加。在连续酒精摄入（CA）三周后，饮酒期间 dynorphin 神经元的钙增加得以维持，但 BNST-CeA 相干性以性别特异性方式发生改变。这些结果表明，BNST 和 CeA 以及 dynorphin 神经元在饮酒行为期间被激活，并且活动动态受刺激新颖性和慢性酒精的影响。
