Psilocybin Attenuates Cortical Representations of Aversion in the Mouse Auditory Cortex.

Summary

Psilocybin selectively reduces responses to aversive stimuli and previously learned aversive-associated tones in the auditory cortex of mice, while not impacting reward responses or new aversive associations. The drug increases coordination among tone-responsive neurons initially but later decreases it specifically among those encoding aversive tones. This indicates that psilocybin dampens established negative sensory representations without broadly affecting auditory processing.

Study at a glance

Abstract

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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