PROJECT SUMMARY Many species, including mice, use ballistic reorienting movements called saccades to actively explore their environment for salient stimuli. Saccades result in a transient modification of visual perception such that it becomes difficult to see visual stimuli which appear around the time of saccades. This phenomenon is called saccadic suppression and it is associated with a decrease in neural activity across the visual system. Converging lines of evidence show that this neural correlate of saccadic suppression arises from a combination of visual and premotor mechanisms. Several studies have shown that the simulating the self-generated motion associated with saccades is sufficient to reduce visual sensitivity in the retina and reproduces the perceptual deficits associated with actual saccades. Complementary studies have hypothesized that the saccade motor plan is broadcast to the visual system where it is used to suppress visual activity during the peri-saccadic epoch. This is supported by studies which demonstrate the persistence of saccadic suppression under conditions which minimize or preclude the effect of visual mechanisms. In this proposal, we seek to understand how the visual and premotor components of saccadic suppression are implemented by neural circuits. We will focus our investigation on the midbrain superior colliculus (SC), a visuomotor brain structure which has long been suspected as the source of a corollary discharge that suppresses visual activity around the time of saccades. We would like to add to this idea that the visual output of the retina is itself modulated by saccades. We hypothesize that a corollary discharge of premotor activity in the SC and the peri-saccadic modulation of retinal signals cooperate to produce suppression of visual activity in the superficial layers of the SC around the time of saccades. In Aim 1 of the proposal, we will dissect the premotor circuitry in the SC using optogenetics, chemogenetics, and high-density in vivo recordings of single-unit activity while mice make saccades. In Aim 2 of this proposal, we will examine SC-projecting retinal ganglion cells for peri-saccadic modulation using two-photon calcium imaging and naturalistic visual stimulation. Public health significance. This proposal aims to understand how saccadic suppression is implemented by dissecting the visual and premotor circuitry in the midbrain SC. This research will advance our understanding of the neural basis for stable and continuous visual perception across saccades which is critical for the conduct of normal visual behavior. In addition, this research could lead to improvements in the diagnosis and treatment of injury and diseases which affect the oculomotor system.