Psilocybin reduces functional connectivity and the encoding of spatial
information by neurons in mouse retrosplenial cortex
Abstract
Psychedelic drugs have profound effects on perception, cognition, and
mood. How psychedelics affect neural signaling to produce these effects
remains poorly understood. We investigated the effect of the classic
psychedelic psilocybin on neural activity patterns and spatial encoding
in the retrosplenial cortex of head-fixed mice navigating on a
treadmill. The place specificity of neurons to distinct locations along
the belt was reduced by psilocybin. Moreover, the stability of
place-related activity across trials decreased. Psilocybin also reduced
the functional connectivity among simultaneously recorded neurons. The
5-HT2AR (serotonin 2A receptor) antagonist ketanserin blocked the
majority of these effects. These data are consistent with proposals that
psychedelics increase the entropy of neural signaling, and provide a
potential neural mechanism contributing to disorientation frequently
reported by humans after taking psychedelics.