A Hallucinogenic Serotonin-2A Receptor Agonist Reduces Visual Response Gain and Alters Temporal Dynamics in Mouse V1

Abstract

Summary: Sensory perception arises from the integration of externally and internally driven representations of the world. Disrupted balance of these representations can lead to perceptual deficits and hallucinations. The serotonin-2A receptor (5-HT2AR) is associated with such perceptual alterations, both in its role in schizophrenia and in the action of hallucinogenic drugs. Despite this powerful influence on perception, relatively little is known about how serotonergic hallucinogens influence sensory processing in the neocortex. Using widefield and two-photon calcium imaging and single-unit electrophysiology in awake mice, we find that administration of the hallucinogenic selective 5-HT2AR agonist DOI (2,5-dimethoxy-4-iodoamphetamine) leads to a net reduction in visual response amplitude and surround suppression in primary visual cortex, as well as disrupted temporal dynamics. However, basic retinotopic organization, tuning properties, and receptive field structure remain intact. Our results provide support for models of hallucinations in which reduced bottom-up sensory drive is a key factor leading to altered perception. : Activation of serotonin-2A receptors (5-HT2ARs) is associated with hallucinations, but impacts on sensory processing are largely unknown. Michaiel et al. demonstrate that the 5-HT2AR agonist DOI strongly reduces sensory-evoked activity and disrupts temporal dynamics. These results support models of hallucinations that propose reduced bottom-up sensory drive. Keywords: visual cortex, serotonin, hallucination, sensory processing, mouse, V1, receptive fields, contextual modulation