UNRAVELing the synergistic effects of psilocybin and environment on brain-wide immediate early gene expression in mice
OpenAlex – February 21, 2023
Source: OpenAlex
Summary
Psilocybin, a potent hallucinogen, profoundly alters brain activity regardless of environment. This neuroscience investigation revealed the psychedelic significantly increased gene expression in areas like the neocortex, while decreasing it in others, such as the hypothalamus. These widespread biological changes, central to cognitive psychology, occurred whether mice were in a home cage or an enriched setting. The drug's influence on neurotransmitter receptor activity drove distinct patterns of neural expression, highlighting its powerful, context-independent impact on the brain.
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.