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bioRxiv · 10.1101/2021.02.17.431629

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

Shao, L.-X.·Liao, C.·Gregg, I.·Savalia, N.·Delagarza, K.·Kwan, A. C.
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Abstract

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 time scale 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 hours 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.

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Shao, L.-X., Liao, C., Gregg, I., Savalia, N., Delagarza, K., Kwan, A. C.. 2021-02-17. Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo. https://doi.org/10.1101/2021.02.17.431629

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