UNRAVELing the synergistic effects of psilocybin and environment on brain-wide immediate early gene expression in mice
Daniel Ryskamp Rijsketic, Austen B. Casey, Daniel A. N. Barbosa, Xue Zhang, Tuuli M. Hietamies, Grecia Ramirez-Ovalle, Matthew B. Pomrenze, Casey H. Halpern, Leanne M. Williams, Robert C. Malenka, Boris D. Heifets
bioRxiv (Cold Spring Harbor Laboratory) February 21, 2023 preprint DOI: 10.1101/2023.02.19.528997 via OpenAlex
Summary
AI-generated from the abstractPsilocybin, given to mice in either their home cage or an enriched environment, increased neural activity in brain regions including the neocortex, caudoputamen, central amygdala, and parasubthalamic nucleus while decreasing activity in the hypothalamus, cortical amygdala, striatum, and pallidum. The effects of both the drug and the environment were strong and widespread but largely independent, with very few interactions between context and psilocybin treatment. This suggests that the brain's response to psilocybin is not strongly modulated by environmental setting at the level of immediate early gene expression.
Study at a glance
| Characteristics | Experimental study |
|---|---|
| Population | Mice |
| Intervention | Psilocybin |
| Topics | Psilocybin |
| Keywords | Expression computer science Neuroscience Gene expression Hallucinogen |
| Citations | 10 |
| Key finding | Psilocybin increased c-Fos expression in the neocortex, caudoputamen, central amygdala, and parasubthalamic nucleus and decreased it in the hypothalamus, cortical amygdala, striatum, and pallidum, with main effects of context and psilocybin being widespread and spatially distinct but interactions surprisingly sparse. |
Abstract
Abstract The effects of context on the subjective experience of serotonergic psychedelics have not been fully examined in human neuroimaging studies, partly due to limitations of the imaging environment. Here, we administered saline or psilocybin to mice in their home cage or an enriched environment, immunofluorescently-labeled brain-wide c-Fos, and imaged cleared tissue with light sheet microscopy to examine the impact of context on psilocybin-elicited neural activity at cellular resolution. Voxel-wise analysis of c-Fos-immunofluorescence revealed differential neural activity, which we validated with c-Fos + cell density measurements. Psilocybin increased c-Fos expression in the neocortex, caudoputamen, central amygdala, and parasubthalamic nucleus and decreased c-Fos in the hypothalamus, cortical amygdala, striatum, and pallidum. Main effects of context and psilocybin-treatment were robust, widespread, and spatially distinct, whereas interactions were surprisingly sparse.