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Abstract Emerging evidence suggests that nitrous oxide (N2O), a gaseous NMDA receptor antagonist and dissociative anesthetic, exerts rapid antidepressant effects akin to subanesthetic ketamine. However, its cellular, molecular, and behavioral effects remain poorly understood. Using in vivo two-photon imaging through cortical microprisms, we demonstrate that 50% N2O/O2 rapidly increases neuronal calcium activity in the mouse medial prefrontal cortex (mPFC).
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