Sex-specific increased reactivity of the PVT and prolonged PVT→CeA circuit engagement following psilocin administration.

Psilocin, the active metabolite of psilocybin, alters brain activity in rats in a sex-specific manner. It increases activity in the paraventricular nucleus of the thalamus (PVT) and selectively engages PVT projections to the central amygdala (CeA) in females but not males. Psilocin enhances PVT reactivity to an aversive stimulus, driven by passive responders, and prevents time-dependent reductions in stimulus-evoked activity in PVT→CeA neurons in females but not males, driven by active responders. These findings identify sex-specific modulation of thalamic-limbic circuitry by psilocin, advancing understanding of how psychedelics modulate emotional brain circuits.

Study at a glance

Abstract

The psychedelic psilocybin has shown therapeutic potential, yet underlying neural mechanisms remain poorly understood. We investigated the impact of psilocin-the active metabolite of psilocybin-on basal activity and reactivity within the paraventricular nucleus of the thalamus (PVT) and PVT projections to central amygdala (CeA) in rats. Psilocin administration increased PVT c-Fos expression and selectively engaged PVT→CeA neurons in females, but not males. Psilocin enhanced PVT reactivity to an aversive air-puff stimulus, with effects primarily driven by passive responders. In PVT→CeA neurons, psilocin prevented time-dependent reductions in stimulus-evoked activity and maintained reactivity across timepoints in females but not males. The sustained engagement of PVT→CeA circuitry was driven by active responders. These findings identify sex-specific modulation of thalamic-limbic circuitry and behavior by psilocin, implicating PVT→CeA circuitry in the neural and behavioral effects of psychedelic compounds, advancing our understanding of how psychedelics modulate emotional brain circuits to further inform potential therapeutic mechanisms.