美国加州大学C. K. Kim团队近期取得重要工作进展，他们研究了分析了抗焦虑行为状态下迷幻反应神经元的工作机理。相关研究成果
据介绍，致幻剂有望成为神经精神疾病的替代疗法。然而，它们驱动适应性行为效应的神经机制尚不清楚。
研究人员分离了受致幻剂调节的特定神经元，以确定它们在驾驶行为中的作用。使用光和钙依赖的活性整合器，研究人员对小鼠内侧前额叶皮层（mPFC）中的迷幻反应神经元进行了遗传学标记。单核RNA测序显示，致幻剂驱动了多种细胞类型的网络水平激活，而不仅仅是表达5-羟色胺2A受体的细胞。
研究人员用兴奋性通道视紫红质标记了迷幻反应的mPFC神经元，以实现其靶向操纵。研究人员发现，这些细胞的再激活再现了致幻剂的抗焦虑作用，而没有驱动其致幻作用。
总之，这一研究揭示了对致幻剂诱导的行为状态背后的细胞类型特异性机制的重要见解。
附：英文原文
Title: Isolation of psychedelic-responsive neurons underlying anxiolytic behavioral states
Author: J. Muir, S. Lin, I. K. Aarrestad, H. R. Daniels, J. Ma, L. Tian, D. E. Olson, C. K. Kim
Issue&Volume: 2024-11-15
Abstract: Psychedelics hold promise as alternate treatments for neuropsychiatric disorders. However, the neural mechanisms by which they drive adaptive behavioral effects remain unclear. We isolated the specific neurons modulated by a psychedelic to determine their role in driving behavior. Using a light- and calcium-dependent activity integrator, we genetically tagged psychedelic-responsive neurons in the medial prefrontal cortex (mPFC) of mice. Single-nucleus RNA sequencing revealed that the psychedelic drove network-level activation of multiple cell types beyond just those expressing 5-hydroxytryptamine 2A receptors. We labeled psychedelic-responsive mPFC neurons with an excitatory channelrhodopsin to enable their targeted manipulation. We found that reactivation of these cells recapitulated the anxiolytic effects of the psychedelic without driving its hallucinogenic-like effects. These findings reveal essential insight into the cell-type–specific mechanisms underlying psychedelic-induced behavioral states.
DOI: adl0666
Source: https://www.science.org/doi/10.1126/science.adl0666