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Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo

2021; Cell Press; Volume: 109; Issue: 16 Linguagem: Inglês

10.1016/j.neuron.2021.06.008

1097-4199

Ling-Xiao Shao, Clara Liao, Ian Gregg, Pasha A. Davoudian, Neil K. Savalia, Kristina Delagarza, Alex C. Kwan,

Chemical synthesis and alkaloids

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.