
==== Front
bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.09.06.611733
preprint
1
Article
The serotonergic psychedelic DOI impairs deviance detection in the auditory cortex
Horrocks Max
Mohn Jennifer L. http://orcid.org/0000-0002-6808-8489

Jaramillo Santiago http://orcid.org/0000-0002-6595-8450

12 9 2024
2024.09.06.611733https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://biorxiv.org/lookup/doi/10.1101/2024.09.06.611733
nihpp-2024.09.06.611733.pdf
Abstract

Psychedelics are known to induce profound perceptual distortions, yet the neural mechanisms underlying these effects, particularly within the auditory system, remain poorly understood. In this study, we investigated the effects of the psychedelic compound 2,5-Dimethoxy-4-iodoamphetamine (DOI), a serotonin 2A receptor agonist, on the activity of neurons in the auditory cortex of awake mice. We examined whether DOI administration alters sound-frequency tuning, variability in neural responses, and deviance detection (a neural process reflecting the balance between top-down and bottom-up processing). Our results show that while DOI does not alter the frequency selectivity of auditory cortical neurons in a consistent manner, it increases trial-by-trial variability in responses and consistently diminishes the neural distinction between expected (standard) and unexpected (oddball) stimuli. This reduction in deviance detection was primarily driven by a decrease in the response to oddball sounds, suggesting that DOI dampens the auditory cortex’s sensitivity to unexpected events. These findings provide insights into how psychedelics disrupt sensory processing and shed light on the neural mechanisms underlying the altered perception of auditory stimuli observed in the psychedelic state.
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pmc
