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Peer-reviewed article

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

Shao LXiD, Liao C, Gregg I, Davoudian PAiD, Savalia NKiD, Delagarza K, Kwan ACiD

NeuronJul 5, 2021United States501 citationsDOI: 10.1016/j.neuron.2021.06.008

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 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.

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Psilocybin

Keywords

SynapseDendritesstructural remodelingAntidepressantPyramidal NeuronNeural PlasticityMedial Prefrontal CortexHallucinogenSerotonergic Psychedelic

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