Short- and long-term reconfiguration of rat prefrontal cortical networks following single doses of psilocybin

Psilocybin at therapeutically relevant doses (0.3 or 1 mg/kg) in rats unmasked 100 Hz high frequency oscillations in the infralimbic cortex that persisted for about an hour, accompanied by decreased pyramidal cell firing rates and reduced signal complexity. These acute effects were more pronounced during rest than during a sustained attention task. Over the following days, gradually emerging increases in beta and low-gamma (20-60 Hz) power appeared specifically in the infralimbic cortex, suggesting network plasticity on multi-day timescales. The findings implicate infralimbic network oscillations as potential biomarkers of psychedelic action not readily detectable in human brain imaging.

Study at a glance

Abstract

SUMMARY 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 (0.3mg/kg or 1mg/kg i.p.) unmasked 100Hz high frequency oscillations that were most pronounced within the infralimbic cortex, persisted for approximately 1h post-injection and were accompanied by decreased net pyramidal cell firing rates and reduced signal complexity. These acute effects were more prominent during resting behaviour than during a sustained attention task. LFP 1-, 2- and 6-days post-psilocybin showed gradually-emerging increases in beta and low-gamma (20-60Hz) 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.