Psilocybin is a serotonergic psychedelic with untapped therapeutic potential. There are hints that the use of psychedelics can produce neural adaptations, although the extent and timescale of the impact in a mammalian brain are unknown. In this study, we used chronic two-photon microscopy to image longitudinally the apical dendritic spines of layer 5 pyramidal neurons in the mouse medial frontal cortex. We found that a single dose of psilocybin led to ∼10% increases in spine size and density, driven by an elevated spine formation rate. The structural remodeling occurred quickly within 24 h and was persistent 1 month later. Psilocybin also ameliorated stress-related behavioral deficit and elevated excitatory neurotransmission. Overall, the results demonstrate that psilocybin-evoked synaptic rewiring in the cortex is fast and enduring, potentially providing a structural trace for long-term integration of experiences and lasting beneficial actions.

赛洛西宾是一种具有未开发治疗潜力的血清素迷幻药。有迹象表明，使用迷幻剂可以产生神经适应，尽管对哺乳动物大脑的影响程度和时间尺度尚不清楚。在这项研究中，我们使用慢性双光子显微镜对小鼠内侧额叶皮层第 5 层锥体神经元的顶端树突棘进行纵向成像。我们发现单剂量的裸盖菇素导致脊柱大小和密度增加约 10%，这是由脊柱形成率升高驱动的。结构重塑在 24 小时内迅速发生，并在 1 个月后持续存在。赛洛西宾还改善了与压力相关的行为缺陷和兴奋性神经传递升高。总体而言，结果表明，psilocybin 诱发的皮层突触重新布线是快速且持久的，