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Psilocybin reduces functional connectivity and the encoding of spatial information by neurons in mouse retrosplenial cortex
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  • Victorita Ivan,
  • David Tomas-Cuesta,
  • Ingrid Esteves,
  • Artur Luczak,
  • Majid Mohajerani,
  • Bruce McNaughton,
  • Aaron Gruber
Victorita Ivan
University of Lethbridge
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David Tomas-Cuesta
University of Lethbridge
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Ingrid Esteves
University of Lethbridge
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Artur Luczak
University of Lethbridge
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Majid Mohajerani
University of Lethbridge
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Bruce McNaughton
Lethbridge University
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Aaron Gruber
University of Lethbridge

Corresponding Author:[email protected]

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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.
Submitted to European Journal of Neuroscience
08 Mar 2024Submission Checks Completed
08 Mar 2024Assigned to Editor
09 Mar 2024Review(s) Completed, Editorial Evaluation Pending
09 Mar 2024Reviewer(s) Assigned
22 Apr 2024Editorial Decision: Revise Major
30 Jul 20241st Revision Received
02 Aug 2024Submission Checks Completed
02 Aug 2024Assigned to Editor
02 Aug 2024Review(s) Completed, Editorial Evaluation Pending
02 Aug 2024Reviewer(s) Assigned
18 Sep 2024Editorial Decision: Accept