The impact of the serotonergic psychedelic DOI on active vision in freely moving mice

Skyberg, R. J.; Fields, C. W.; Martins, D. M.; Niell, C. M.

doi:10.1101/2025.10.14.682230

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bioRxiv · 10.1101/2025.10.14.682230

The impact of the serotonergic psychedelic DOI on active vision in freely moving mice

Skyberg, R. J.·Fields, C. W.·Martins, D. M.·Niell, C. M.

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Abstract

Psychedelics offer a unique opportunity to investigate the neural mechanisms governing both normal and altered perceptual states, yet relatively little is known about their impact on visual processing at the level of neural coding, particularly in the context of active vision. Here we examined how the serotonergic psychedelic DOI (2,5-dimethoxy-4-iodoamphetamine) influences neural activity within the visual cortex (V1) of freely moving mice engaged in naturalistic vision. Previous work has demonstrated that, under normal conditions, gaze shifts trigger a temporal sequence in V1 that encodes visual information in a coarse-to-fine sequence. Here we found that DOI had a diverse and temporally dynamic impact on response amplitudes across this sequence -- while net population-level firing was modestly suppressed, individual neurons showed large increases or decreases in their gaze shift responses. Strikingly, this bidirectional modulation was correlated with gaze-shift response latency. DOI had mixed effects on short latency, low spatial frequency preferring neurons, but became increasingly suppressive across the sequence, ultimately suppressing nearly all long latency, high spatial frequency preferring neurons. These findings demonstrate how psychedelics disrupt naturalistic visual processing and support a framework in which visual hallucinations result from an imbalance in coarse and fine input integration during active vision. HighlightsO_LIWe recorded neural activity from V1 of freely moving mice before and after administration of the psychedelic DOI. C_LIO_LIDOI had diverse effects on visual response amplitude following a gaze shift, with some neurons increasing while others decreased. C_LIO_LIThe modulation of responses was temporally dynamic, shifting across the response sequence. C_LIO_LILonger latency neurons, which preferentially encode high spatial frequency information, were more consistently suppressed C_LIO_LITogether these effects result in a disruption of population response and coarse-to-fine processing, providing potential mechanisms for altered visual perception C_LI

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Skyberg, R. J., Fields, C. W., Martins, D. M., Niell, C. M.. 2025-10-15. The impact of the serotonergic psychedelic DOI on active vision in freely moving mice. https://doi.org/10.1101/2025.10.14.682230

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