Psychedelic drugs such as psilocybin reduce the place specificity of neurons in the retrosplenial cortex of mice navigating a treadmill, making neural activity less tied to distinct locations. The stability of place-related activity across trials also decreases, and functional correlations among simultaneously recorded neurons are lowered. These effects are blocked by the serotonin 2A receptor antagonist ketanserin, indicating that the 5-HT2A receptor mediates them. The findings suggest that psychedelics increase the entropy of neural signaling, which may contribute to the disorientation often reported by humans after taking psychedelics.
Psilocybin, a classic psychedelic, reduces the spatial specificity and stability of neural activity in the retrosplenial cortex of mice navigating a treadmill. Place-related firing of neurons became less selective for distinct locations, and the consistency of this activity across trials decreased. Functional connectivity between simultaneously recorded neurons also declined. Most of these effects were blocked by the serotonin 2A receptor antagonist ketanserin, implicating 5-HT2AR signaling. The findings align with the proposal that psychedelics increase neural entropy and may explain the disorientation often reported by humans after taking such drugs.