Psilocybin reduces functional connectivity and the encoding of spatial information by neurons in mouse retrosplenial cortex
Victorita E. Ivan, David P. Tomàs‐cuesta, Ingrid M. Esteves, Artur Luczak, Majid H. Mohajerani, Bruce L. Mcnaughton, Aaron J. Gruber
April 22, 2024 DOI: 10.22541/au.171378690.00112411/v1 via OpenAlex
Summary
AI-generated from the abstractPsilocybin, 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.
Study at a glance
| Characteristics | Experimental study |
|---|---|
| Population | Head-fixed mice navigating on a treadmill |
| Interventions | Psilocybin Ketanserin |
| Topics | Psilocybin |
| Keywords | Retrosplenial cortex Neuroscience Hallucinogen Psychology |
| Citations | 1 |
| Key finding | Psilocybin reduced the place specificity, stability, and functional connectivity of neural activity in the retrosplenial cortex of mice, effects largely blocked by ketanserin. |
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.