美国宾夕法尼亚大学Gregory Corder小组宣布他们的最新研究揭示了裸盖菇素增强的恐惧消退与皮质集合的双向调节有关。相关论文于2025年5月26日发表于国际顶尖学术期刊《自然—神经科学》杂志上。

为了测试裸盖菇素是否通过改变皮质神经系统的活动来增强行为灵活性，该团队在为期5天的追踪恐惧学习和消退实验中对无主题的脾脏后皮层进行了纵向单细胞钙成像。研究组发现单剂量的裸盖菇素改变了皮质集合转换，并相反地调节了恐惧和灭绝活性神经元。恐惧活性神经元的抑制和灭绝活性神经元的募集预示着裸盖菇碱增强的恐惧消退。在该微电路的计算模型中，抑制模拟的恐惧活跃单元调节了灭绝活跃单元的招募和冻结时的行为变化，与实验结果一致。这些结果表明，裸盖菇素通过在脾后皮层招募新的神经元群和抑制恐惧活跃的群体来增强行为灵活性。

研究人员表示，迷幻药裸盖菇素在以行为不灵活为特征的神经精神疾病中表现出快速和持久的疗效。然而，它对行为灵活性持续变化的神经活动的影响尚未被表征。

附：英文原文

Title: Psilocybin-enhanced fear extinction linked to bidirectional modulation of cortical ensembles

Author: Rogers, Sophie A., Heller, Elizabeth A., Corder, Gregory

Issue&Volume: 2025-05-26

Abstract: The psychedelic drug psilocybin demonstrates rapid and long-lasting efficacy across neuropsychiatric disorders that are characterized by behavioral inflexibility. However, its impact on the neural activity underlying sustained changes in behavioral flexibility has not been characterized. To test whether psilocybin enhances behavioral flexibility by altering activity in cortical neural ensembles, we performed longitudinal single-cell calcium imaging in the mouse retrosplenial cortex across a 5-day trace fear learning and extinction assay. We found that a single dose of psilocybin altered cortical ensemble turnover and oppositely modulated fear- and extinction-active neurons. Suppression of fear-active neurons and recruitment of extinction-active neurons predicted psilocybin-enhanced fear extinction. In a computational model of this microcircuit, inhibition of simulated fear-active units modulated recruitment of extinction-active units and behavioral variability in freezing, aligning with experimental results. These results suggest that psilocybin enhances behavioral flexibility by recruiting new neuronal populations and suppressing fear-active populations in the retrosplenial cortex.

DOI: 10.1038/s41593-025-01964-9

Source: https://www.nature.com/articles/s41593-025-01964-9