Psilocybin Attenuates Cortical Representations of Aversion in the Mouse Auditory Cortex.
James D. Johnson, Runyi Tian, Yasaman Etemadi, Zheng Li
bioRxiv : the preprint server for biology March 27, 2026 preprint DOI: 10.64898/2026.03.26.714498 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Longitudinal two-photon calcium imaging study |
|---|---|
| Population | Awake C57BL/6 mice |
| Intervention | Psilocybin |
| Topics | Psilocybin |
| Keywords | Auditory cortex Aversive Psychedelic Valence |
| Key findings | Psilocybin selectively reduces responses to aversive stimuli and earlier-established aversive-associated tones in auditory cortex without affecting reward responses or new aversive learning. |
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.
Comparable studies
Other preclinical and animal studies on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice Mice | 2021 | Experimental study | |
| Psychedelics reopen the social reward learning critical period Mice | 2023 | Experimental study in mice | |
| Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice | 2020 | Experimental study with dose-response experiments | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study |
Citations in the library
Cites 29
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin Proceedings of the National Academy of Sciences January 23, 2012
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics Pharmacological Reviews June 20, 2019
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
and 24 more in the library