bioRxiv : the preprint server for biologyApr 3, 2026

Psilocybin reduces brain responses to unpleasant sounds in the mouse hearing system

Psychedelic Science Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

Psilocybin dampened well consolidated aversive sound representations in mouse auditory cortex without broadly changing auditory processing or new aversive learning.

Evidence

Longitudinal two-photon calcium imaging tracked layer 2/3 auditory cortex responses in awake C57BL/6 mice after tones, reward stimuli, aversive stimuli, and valence-associated tones.

Caveat

The evidence comes from a mouse sensory-cortex model and distinguishes earlier-established from newly learned aversive associations, not human affective outcomes.

Simplified

Psilocybin can produce sustained benefits in affective and trauma-related disorders, yet if and how it reshapes sensory representations of learned valence associations remains largely unclear. To address this, we used longitudinal two-photon calcium imaging in awake C57BL/6 mice to examine how psilocybin modulates layer 2/3 auditory cortex activity at single-cell and population levels. Evoked responses were measured for tones with or without prior associations with valenced stimuli, as well as for the valenced stimuli themselves. Most responsive neurons were selective for tones alone, while distinct subsets responded exclusively to reward or aversive stimuli, and a smaller population encoded both. Psilocybin selectively reduced responses to aversive stimuli and earlier-established aversive-associated tones, without affecting aversive association, reward responses, or responses to newly aversive-associated tones. At the population level, psilocybin acutely increased coordination across tone-responsive neurons, while later reducing it selectively among neurons encoding the aversive-associated tone. These results demonstrate that psilocybin preferentially dampens well consolidated aversive sensory representations in auditory cortex, rather than fresh associations, without broadly affecting auditory processing or new aversive learning.

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Psilocybin reduces brain responses to unpleasant sounds in the mouse hearing system

Abstract

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