Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo
Ling-Xiao Shao, Clara Liao, Ian Gregg, Pasha A. Davoudian, Neil K. Savalia, Kristina Delagarza, Alex C. Kwan
Neuron July 5, 2021 DOI: 10.1016/j.neuron.2021.06.008 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Population | Mice |
| Intervention | Psilocybin |
| Topics | Psilocybin Serotonin |
| Keywords | Dendritic spine Cortex anatomy Hallucinogen Neurotransmission Excitatory postsynaptic potential Infralimbic cortex Prefrontal cortex Inhibitory postsynaptic potential Hippocampal formation Biochemistry |
| Citations | 589 |
| Key findings | A single dose of psilocybin led to a ∼10% increase in spine size and density in the mouse medial frontal cortex, driven by elevated spine formation, with changes occurring within 24 hours and persisting for at least one month. |
Abstract
Summary 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.