PROJECT SUMMARY/ABSTRACT Humans, like all primates, use both eyes in tandem to compute a perceptual interpretation of the visual world. However, binocular vision often fails, causing some of the most common visual disorders such as amblyopia, strabismus, diplopia or stereoblindness. Collectively, binocular visual deficits affect ~10-20% of the population, and the associated problems are generally intractable. Unraveling the neural circuitry that performs binocular integration, which is the goal of the present project, is a critical stepping-stone for developing novel and effec- tive therapeutic approaches. Here, we will fill a pressing gap in our current knowledge about the brain locations and mechanisms that support interocular interactions (cross-talk) between the retinal output of the two eyes. It is still unclear whether the two eyes' signals first meet in the cortex or already interact subcortically. While some data collected in anesthetized cats point to early cross-talk between the two eyes' signals within the tha- lamic relay, other data suggest that this is not the case. The goal of this grant is to resolve the uncertainty be- tween these two alternative possibilities. We will address the question whether there is cross-talk between the two monocular channels before the level of V1 using an innovative, integrative approach that combines simul- taneous multi-electrode array recordings with targeted neuropharmacological and optogenetic interventions. We will answer two fundamental questions. First, we will determine the degree of binocularity of M, P and K neurons in the LGN. We will do so using LGN recordings combined with cell-type specific optogenetics in awake macaques confronted with varying contrast levels during binocular stimulation. As a second step, we will eliminate feedback to the LGN by reversibly inactivating V1. Using laminar arrays, we will determine the residual activity in LGN as well as the current flow in inactivated cortex, which provides a measure of LGN feedforward inputs to V1. The outcome of all experiments combined will conclusively determine the respective roles of primate LGN and V1 for binocular integration, which is of great significance for our general understand- ing of primate vision and associated clinical implications. Without resolving these questions, models of binocu- lar vision will be incomplete or inaccurate, which will hamper medical progress for correcting disorder of bin- ocular vision, such as amblyopia and stereoblindness, which collectively affect one out of every ten people worldwide.