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Isolation of psychedelic responsive neurons underlying anxiolytic behavioral states

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE278644 | GEO | 2024/11/04

REPOSITORIES: GEO

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Isolation of psychedelic responsive neurons underlying anxiolytic behavioral states

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