Psilocybin Attenuates Cortical Representations of Aversion in the Mouse Auditory Cortex.
bioRxiv : the preprint server for biology March 27, 2026 James D. Johnson, Runyi Tian, Yasaman Etemadi et al.
Psilocybin preferentially dampens well-consolidated aversive sensory representations in the auditory cortex, rather than fresh associations, without broadly affecting auditory processing or new aversive learning. Using longitudinal two-photon calcium imaging in awake mice, psilocybin selectively reduced responses to aversive stimuli and earlier-established aversive-associated tones, while reward responses and responses to newly aversive-associated tones remained unaffected. At the population level, psilocybin acutely increased coordination across tone-responsive neurons, then later reduced it selectively among neurons encoding the aversive-associated tone. These results suggest psilocybin reshapes sensory representations of learned valence associations, potentially explaining its benefits in affective and trauma-related disorders.