A Snapshot seminar hosted by the School of Physiology, Pharmacology and Neuroscience
Abstract: Introduction: There is a resurging interest in the therapeutic value of psychedelic drugs for treatment of mental health problems such as depression. Despite this, little is known of the neural mechanisms underlying the effects of these drugs. Psilocybin is a classical psychedelic which acts on the serotonergic (5-HT) system and has strong affinity to 5-HT2A receptors which are highly expressed in the prefrontal cortex (PFC). In this study we aimed to define a cellular-resolution map of psilocybin-induced network dynamics in the PFC.
Methods: Using Neuropixels silicon probes, we recorded local field potential and spiking activity from large populations of neurons across the entire medial prefrontal cortex of awake, freely moving rats. Rats were given a psilocybin injection (0.3mg/kg) before completing a task of sustained attention, interleaved with periods of rest. Subsequent recordings were taken on days 1, 2 and 6 post-injection with the same protocol repeated with saline injections after a 1-week washout period in a counterbalanced design.
Results: Psilocybin led to the emergence of an anatomically localised ~100Hz high frequency oscillation (HFO). Spiking activity from over 1600 stable units revealed a significant reduction in firing rates yet increased cross-correlated activity between pairs of pyramidal cells. Psilocybin’s effects on neural activity also showed state-dependence, largely evident only during the disengaged rest periods compared to active task engagement.
Discussion: We show that psilocybin alters both local network and cellular activity with emergence of a HFO which may reflect increased intra-prefrontal synchronisation and a potential biological marker of psychedelic experience. The state-dependent nature of these effects corroborates clinical application of psilocybin under low-stimuli environments