Alcohol abuse and alcohol dependence are key factors in the development of alcohol use disorder, which is a pervasive societal problem with substantial economic, medical, and psychiatric consequences. Although our understanding of the neurocircuitry that underlies alcohol use has improved, novel brain regions that are involved in alcohol use and novel biomarkers of alcohol use need to be identified. The present study used a single-cell whole-brain imaging approach to 1) assess whether abstinence from alcohol in an animal model of alcohol dependence alters the functional architecture of brain activity and modularity, 2) validate our current knowledge of the neurocircuitry of alcohol abstinence, and 3) discover brain regions that may be involved in alcohol use. Alcohol abstinence resulted in the whole-brain reorganization of functional architecture in mice and a pronounced decrease in modularity that was not observed in nondependent moderate drinkers. Structuring of the alcohol abstinence network revealed three major brain modules: 1) extended amygdala module, 2) midbrain striatal module, and 3) cortico-hippocampo-thalamic module, reminiscent of the three-stage theory. Many hub brain regions that control this network were identified, including several that have been previously overlooked in alcohol research. These results identify brain targets for future research and demonstrate that alcohol use and dependence remodel brain-wide functional architecture to decrease modularity. Further studies are needed to determine whether the changes in coactivation and modularity that are associated with alcohol abstinence are causal features of alcohol dependence or a consequence of excessive drinking and alcohol exposure.

中文翻译：

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通过酒精依赖和节制来重塑大脑功能结构。

酗酒和酗酒是导致酗酒障碍的关键因素，这是一个普遍存在的社会问题，具有重大的经济，医学和精神方面的后果。尽管我们对酒精使用所基于的神经回路的理解已有所改善，但仍需要确定涉及酒精使用的新型大脑区域和酒精使用的新型生物标记。本研究使用单细胞全脑成像方法来进行以下研究：1）在酒精依赖动物模型中评估戒酒是否会改变大脑活动和模块性的功能结构，2）验证我们目前对戒酒神经回路的认识，以及3）发现可能与饮酒有关的大脑区域。戒酒会导致小鼠功能结构的全脑重组，模块性显着下降，这在非依赖型中度饮酒者中没有观察到。戒酒网络的结构揭示了三个主要的大脑模块：1）扩展的杏仁核模块，2）中脑纹状体模块，以及3）皮质-海马-丘脑模块，让人联想到三阶段理论。确定了控制该网络的许多中枢大脑区域，包括先前在酒精研究中被忽略的一些区域。这些结果确定了未来研究的大脑目标，并证明了酒精的使用和依赖性会重塑大脑范围的功能体系以降低模块性。