サイケデリック薬が脳細胞に与える広範な影響を発見(Psychedelics alter more brain cells than expected)

2025-09-29 ミシガン大学

<関連情報>

• https://news.umich.edu/psychedelics-alter-far-more-neurons-than-expected/
• https://www.nature.com/articles/s41380-025-03257-w

5-HT2A受容体を欠損した皮質ニューロンのサイケデリックな神経可塑性 Psychedelic neuroplasticity of cortical neurons lacking 5-HT2A receptors

Tyler G. Ekins,Chloe Rybicki-Kler,Tao Deng,Isla A. W. Brooks,Izabela Jedrasiak-Cape,Ethan Donoho & Omar J. Ahmed
Molecular Psychiatry  Published:16 September 2025
DOI:https://doi.org/10.1038/s41380-025-03257-w

Abstract

Classical psychedelic drugs show promise as a treatment for major depressive disorder and related psychiatric disorders. This therapeutic efficacy stems from long-lasting psychedelic-induced neuroplasticity onto prefrontal cortical neurons and is thought to require the postsynaptic expression of serotonin 2A receptors (5-HT_2AR). However, other cortical regions such as the granular retrosplenial cortex (RSG) – important for memory, spatial orientation, fear extinction, and imagining oneself in the future, but impaired in Alzheimer’s disease – lack 5-HT_2AR and are thus considered unlikely to benefit from psychedelic therapy. Here, we show that RSG pyramidal cells lacking postsynaptic 5-HT_2A receptors still undergo long-lasting psychedelic-induced synaptic enhancement. A newly engineered CRISPR-Cas-based conditional knockout mouse line reveals that this form of psychedelic-induced retrosplenial plasticity requires presynaptic 5-HT_2A receptors expressed on anterior thalamic axonal inputs to RSG. These results highlight a broader psychedelic therapeutic utility than currently appreciated, suggesting potential for augmenting RSG circuit function in Alzheimer’s disease, post-traumatic stress disorder, and other neuropsychiatric conditions, despite the lack of postsynaptic 5-HT_2A receptors.