RT Journal Article SR Electronic T1 Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.02.17.431629 DO 10.1101/2021.02.17.431629 A1 Ling-Xiao Shao A1 Clara Liao A1 Ian Gregg A1 Pasha A. Davoudian A1 Neil K. Savalia A1 Kristina Delagarza A1 Alex C. Kwan YR 2021 UL http://biorxiv.org/content/early/2021/06/02/2021.02.17.431629.abstract AB 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.Competing Interest StatementA.C.K. received psilocybin from the investigational drug supply program at Usona Institute, a non-profit organization. The authors declare no other competing interests.