Psilocybin alters how the auditory cortex balances internally generated neural activity against incoming sound-driven signals, based on two-photon imaging of awake mice. This modulation may help explain why musical experience during psilocybin-assisted therapy predicts treatment outcomes for neuropsychiatric conditions.
Psilocybin, a serotonergic psychedelic, alters sensory cortex activity in awake mice in a biphasic manner. A 2 mg/kg dose initially increased both behavioral activity and neural responses to sound. Thirty minutes later, mice became behaviorally hypoactive and cortical responses to sound decreased, while neural response variance and noise correlations increased. Neuronal selectivity for auditory stimuli remained stable. The results suggest psilocybin modulates the balance between intrinsic and stimulus-driven neural activity in sensory cortex, preserving fundamental sensory processing while potentially providing a basis for auditory hallucinations at the level of neuronal micro-circuits.