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Isolation of psychedelic responsive neurons underlying anxiolytic behavioral states

GSE278644 Mus musculus Expression profiling by high throughput sequencing 4 samples Submitted 2024/11/04 Platform GPL24247
Summary
Psychedelics hold promising potential as alternate treatments for neuropsychiatric disorders. However, the neural mechanisms by which they drive adaptive behavioral effects remain unclear. We isolated the specific neurons modulated by a psychedelic to determine their role in driving behavior. Using a light- and calcium-dependent activity integrator, we genetically tagged psychedelic-responsive neurons in the medial prefrontal cortex (mPFC) of mice. Single-nucleus RNA sequencing revealed that the psychedelic drove network-level activation of multiple cell-types, beyond those expressing 5-hydroxytryptamine 2A receptors. We labeled psychedelic-responsive mPFC neurons with an excitatory channelrhodopsin to enable their targeted manipulation. We found that reactivation of these cells recapitulated the anxiolytic effects of the psychedelic, without driving its hallucinogenic-like effects. These findings reveal essential insight into the cell-type specific mechanisms underlying psychedelic-induced behavioral states.
Published in
Isolation of psychedelic-responsive neurons underlying anxiolytic behavioral states
Muir J, Lin S, Aarrestad IK et al. · Science (New York, N.Y.) 2024 · PMID 39541450 · doi:10.1126/science.adl0666
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Also filed as BioProject PRJNA1168133 and SRA study SRP536266. Searching any of these in the dataset finder brings you back here.

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