Psilocybin reduces functional correlation and the encoding of spatial information by neurons in mouse retrosplenial cortex

European Journal of Neuroscience  – October 04, 2024

Source: OpenAlex

Summary

Psilocybin, a classic hallucinogen, profoundly disrupts spatial perception by altering activity in the retrosplenial cortex. Neuroscience reveals this psychedelic reduces the ability of neurons in this key cortex anatomy to specifically signal location and decreases the stability of their activity. This finding, crucial for Psychology and Psychedelics and Drug Studies, suggests a mechanism for disorientation. Biochemical analysis showed these effects are mediated by neurotransmitter receptor influence on behavior, specifically the serotonin 2A receptor. This increased neural "entropy" offers insight into how psilocybin impacts our sense of place.

Abstract

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 correlation among simultaneously recorded neurons. The 5‐HT 2A R (serotonin 2A receptor) antagonist ketanserin blocked 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.

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