2025年6月10日出版的《自然—神经科学》杂志发表了美国马萨诸塞大学Gilles E. Martin研究团队的最新成果，他们开发出小鼠内侧眶额叶皮质抑制神经元集合对酗酒的抑制。

该团队在无主题内侧眶额皮质（mOFC）中发现了一个离散的GABA能神经元集合，该神经元在对酗酒做出反应时选择性地募集，并限制进一步的饮酒行为。该人群的光遗传沉默或消融导致不受控制的酗酒。这种神经元集合是酒精所特有的，而不是其他有益物质所招募的。这个集合中的神经元广泛分布在整个大脑中，但专门分布在丘脑中背侧的突起调节着酗酒。总之，这些结果确定了mOFC中的一个脑回路，该回路通过减少酒精摄入量来防止酗酒，这可能为开发mOFC神经元集合干预措施提供了途径。

据了解，酒精消费仍然是一个重大的全球健康挑战，每年直接和间接导致数百万人死亡。酒精会使前额叶皮层活动失调，但对特定前额叶回路的影响仍有待阐明。

附：英文原文

Title: Suppression of binge alcohol drinking by an inhibitory neuronal ensemble in the mouse medial orbitofrontal cortex

Author: Gimenez-Gomez, Pablo, Le, Timmy, Zinter, Max, MAngale, Peter, Duran-Laforet, Violeta, Freels, Timothy G., Pavchinskiy, Rebecca, Molas, Susanna, Schafer, Dorothy P., Tapper, Andrew R., Thomson, Travis, Martin, Gilles E.

Issue&Volume: 2025-06-10

Abstract: Alcohol consumption remains a significant global health challenge, directly and indirectly causing millions of deaths annually. Alcohol abuse causes dysregulated activity of the prefrontal cortex, yet effects on specific prefrontal circuits remain to be elucidated. Here, we identify a discrete GABAergic neuronal ensemble in the mouse medial orbitofrontal cortex (mOFC) that is selectively recruited in response to binge alcohol drinking and limits further drinking behavior. Optogenetic silencing of this population, or its ablation, results in uncontrolled binge alcohol consumption. This neuronal ensemble is specific to alcohol and is not recruited by other rewarding substances. Neurons in this ensemble project widely throughout the brain, but projections specifically to the mediodorsal thalamus regulate binge alcohol drinking. Together, these results identify a brain circuit in the mOFC that serves to protect against binge drinking by reducing alcohol intake, which may offer avenues for the development of mOFC neuronal ensemble-targeted interventions.

DOI: 10.1038/s41593-025-01970-x

Source: https://www.nature.com/articles/s41593-025-01970-x