Project Summary/Abstract How visual information is processed and transformed in the nervous system is a fundamental question in vision research. Given its clear importance in visually guided behaviors and the available tools, the mouse superior colliculus holds great promise for understanding visual processing and its neural mechanisms. The superior colliculus is a midbrain structure important for multimodal integration and sensorimotor transformation, with its superficial layers receiving direct inputs from the retina. This proposal aims to study how different types of neurons in the superficial superior colliculus (sSC) process visual information, especially in response to more complicated and naturalistic stimuli. Aim 1 is to confirm that cerebellin 4 positive (Cbln4+) neurons are inhibitory and direction selective and to characterize their morphology and synaptic connectivity. The activity of Cbln4+ neurons will then be manipulated to test the hypothesis that inhibitory neural circuits in the sSC mediate contextual modulation in visual motion processing. Aim 2 is to reveal how sSC neurons respond to visual stimuli in a virtual reality environment, with a focus on excitatory and inhibitory direction selective neurons and the wide field vertical neurons which project to the pulvinar thalamic nucleus. Their responses will be studied using in vivo 2-photon Ca2+ imaging and compared between the “closed-loop” (where the animal’s running speed controls the flow of visual scenes) and “open-loop” (where the visual flow is uncoupled from the animal’s locomotion) configurations. These experiments will test the hypothesis that there is a cell-type-specific encoding of self- generated visual flow in the sSC. Aim 3 is to determine whether there are neurons in the sSC that signal the animal’s own locomotion. These non-visual neurons will be fully characterized, and their molecular identity revealed. Finally, physiological recording will be performed to determine whether the sSC displays a depth- specific and location-dependent organization in encoding the animal’s own locomotion and comparing between predicted optic flow and actual visual motion. Together, these experiments will generate important data needed for a complete understanding of visual processing in the brain. Because normal visual processing is compromised in a number of neurological and psychiatric disorders, such as dyslexia, schizophrenia, and autism spectrum disorders, the proposed studies will provide novel insights for the understanding and treatment of these disorders.