Muir, J., Lin, S., Aarrestad, I. K., Daniels, H. R., Ma, J., Tian, L., Olson, D. E., & Kim, C. K. (2024). Isolation of psychedelic-responsive neurons underlying anxiolytic behavioral states. Science (New York, N.Y.), 386(6723), 802\u2013810.<\/a>
<\/p>\n\n\n\nAbstract
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.<\/p>\n\n\n\n
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