Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo
- Neuron. 2021 Aug 18;109(16):2535-2544.e4. doi: 10.1016/j.neuron.2021.06.008.
- 1. Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA.
- 2. Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT 06511, USA.
- 3. Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT 06511, USA; Medical Scientist Training Program, Yale University School of Medicine, New Haven, CT 06511, USA.
- 4. Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA; Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT 06511, USA; Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06511, USA. Electronic address: [email protected].
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.