Seminars
Psilocybin is a serotonergic psychedelic with growing interest as a psychiatric therapeutic, yet how it reshapes brain activity and perception at the circuit level remains poorly understood. I will present two complementary studies from head-fixed mouse models that combine large-scale electrophysiology with behavior to address this question. The first study characterizes how a single dose of psilocybin alters firing rates, local field potentials, EEG oscillations, and burst dynamics across cortical (prefrontal, sensory), hippocampal, and thalamic regions, comparing psilocybin to saline controls and to a ketanserin pre-treatment group that isolates effects dependent on the 5-HT2A receptor. The second study found that psilocybin collapsed performance in a visual change-detection task to chance level while leaving motor kinematics unperturbed, yet, surprisingly, without impairing visual coding itself. Instead, psilocybin biased visual cortex toward sensory surprise by aberrantly recruiting change-encoding neurons even when no change occurred, an effect linked to a prominent 4-Hz oscillation strongest in somatostatin-expressing (SST) interneurons. Together, these studies link psilocybin's receptor pharmacology to circuit-level dynamics and their behavioral/perceptual consequences.
