Isolation of psychedelic-responsive neurons underlying anxiolytic behavioral states.
Jessie Muir, S Lin, Isak K Aarrestad, H R Daniels, J Ma, L Tian, David E. Olson, C K Kim
Science (New York, N.Y.) November 15, 2024 DOI: 10.1126/science.adl0666 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Citations | 37 |
| Key findings | Reactivation of psychedelic-responsive neurons in the medial prefrontal cortex recapitulated the anxiolytic effects of the psychedelic without producing hallucinogenic-like effects. |
Abstract
Psychedelics hold promise 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 just 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.