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, Seán Froudist‐walsh, Matthew W. Jones
Molecular Psychiatry August 26, 2025 DOI: 10.1038/s41380-025-03182-y via OpenAlex
Summary
AI-generated from the abstractAfter a therapeutically relevant dose of psilocybin, high-frequency oscillations at 100 Hz appear in the infralimbic cortex of rats, lasting about an hour, while overall neuron firing rates and spike-train complexity decrease. These acute effects are stronger when the animal is at rest than during a sustained attention task. Over the following days, power in beta and low-gamma frequencies (20–60 Hz) gradually increases in the infralimbic cortex. The findings point to infralimbic network oscillations as potential markers of psychedelic-induced plasticity that unfold over multiple days, revealing details not easily seen in human brain imaging.
Study at a glance
| 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 Neuroscience Term time |
| Citations | 2 |
| Key finding | 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.