Short- and long-term modulation of rat prefrontal cortical activity following single doses of psilocybin
Molecular Psychiatry – August 26, 2025
Source: OpenAlex
Summary
The hallucinogen psilocybin acutely triggers intense 100 Hz brain oscillations in rat prefrontal cortex, across hundreds of neurons. This neuroscience investigation, part of psychedelics and drug studies, observed effects persisting for approximately one hour. Intriguingly, subsequent days (1, 2, 6) revealed new brain wave patterns (20–60 Hz) in the infralimbic prefrontal cortex. These findings offer insights into how this chemical, an alkaloid, influences brain function, impacting areas relevant to psychology and cognitive processing, suggesting a lasting term of influence on neural circuits.
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.