Short- and long-term modulation of rat prefrontal cortical activity following single doses of psilocybin
Ross J. Purple, Rahul Gupta, Christopher W. Thomas, Caroline T. Golden, Nicola Palomero-Gallagher, Robin Carhartt-Harris, Sean Froudist-Walsh, Matthew W. Jones
Molecular Psychiatry August 26, 2025 DOI: 10.1038/s41380-025-03182-y (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Population | Adult rats |
| Intervention | Psilocybin |
| Dose | 0.3 mg/kg or 1 mg/kg i.p. |
| Duration | 6 days post-injection |
| Topics | Psilocybin |
| Keywords | Hallucinogen Prefrontal cortex Term time Cognitive psychology Cognition |
| Citations | 2 |
| Key findings | Psilocybin induces 100 Hz oscillations in the infralimbic cortex and reduces neuronal firing rates acutely, followed by days-long increases in beta and low-gamma power in the same region. |
Abstract
Abstract We quantify cellular- and circuit-resolution neural network dynamics following therapeutically relevant doses of the psychedelic psilocybin. Using chronically implanted Neuropixels probes, we recorded local field potentials (LFP) alongside action potentials from hundreds of neurons spanning infralimbic, prelimbic and cingulate subregions of the medial prefrontal cortex of freely-behaving adult rats. Psilocybin (0.3 mg/kg or 1 mg/kg i.p.) unmasked 100 Hz high frequency oscillations that were most pronounced within the infralimbic cortex, persisted for approximately 1 h post-injection and were accompanied by decreased net neuronal firing rates and reduced spike-train complexity. These acute effects were more prominent during resting behaviour than during performance of a sustained attention task. LFP 1-, 2- and 6-days post-psilocybin showed gradually-emerging increases in beta and low-gamma (20–60 Hz) power, specific to the infralimbic cortex. These findings reveal features of psychedelic action not readily detectable in human brain imaging, implicating infralimbic network oscillations as potential biomarkers of psychedelic-induced network plasticity over multi-day timescales.