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

Abstract

Psychedelic compounds have the ability to generate altered states of consciousness and profoundly distort perception, often resulting in visual hallucinations. While psychedelics have recently regained attention for their potential cognitive and therapeutic effects, how these drugs affect visual processing to generate visual distortions and hallucinations is not as well characterized. Furthermore, studies investigating the effect of psychedelics on visual function have all been performed using head-fixed preparations, preventing animals from engaging in the natural visual behaviors that the visual system evolved to support. To determine the impact of psychedelics on active vision, we recorded neural activity in primary visual cortex (V1) of mice during free movement, while simultaneously recording eye and head position, before and after administration of the serotonergic psychedelic DOI (2,5-dimethoxy-4-iodoamphetamine). We find that DOI increases the frequency of visual active sensing behaviors during free movement and leads to a net reduction in the visually-evoked activity that these behaviors generate in V1. The effect of DOI was highly diverse across the population of V1 neurons, driving suppression and facilitation of visual responses in a laminar specific manner. Finally, the effects of DOI were dependent upon both visual input and the statistics of the stimulus. We found a striking dissociation between impact on gaze shift responses and flashed sparse noise presented during head-fixation, which may reflect predictability of the stimulus. These findings provide insights into how psychedelics disrupt sensory processing and the neural mechanisms underlying these altered perceptual states. We recorded neural activity from the primary visual cortex (V1) of freely moving mice before and after administration of the psychedelic DOI.During free movement, DOI increased the frequency of active sampling behaviors but left the structure of these behaviors intact.The effect of DOI on visual responses following visual active sensing behaviors during free movement was on average suppressive but highly variable on a cell by cell basis.DOI did not alter the coarse-to-fine temporal pattern of visual activity in V1 that is evoked by gaze shifts.The effect of DOI was larger on responses to a head-fixed sparse noise stimulus than to freely-moving gaze shifts, perhaps due to its unpredictability.