Project Summary/Abstract Optimal functioning of the nervous system requires selective wiring of neural circuits, the precision of which is achieved through experience-dependent refinement after birth. A classic model system of experience- dependent neural development is ocular dominance plasticity in the visual system, where monocular visual deprivation in a critical period of early life alters cortical responses. The investigators have recently discovered that normal binocular vision in the critical period drives the matching of orientation preference between the two eyes in the visual cortex, thus revealing a physiological purpose for critical period plasticity in normal development. The proposed experiments aim to study cortical and thalamic mechanisms that underlie the binocular matching process. In aim one, two-photon calcium imaging will be performed chronically to reveal how individual cortical cells change their monocular orientation tunings to match between the two eyes. In addition, two-photon imaging and electrophysiological recording will be used to characterize the binocular response properties of subtypes of inhibitory neurons before, during, and after the critical period. In aim two, electrophysiological recordings will be conducted to determine whether there are more binocular neurons in the dorsal lateral geniculate nucleus (dLGN) of young mice than in adults, and whether these binocular dLGN neurons show significant matching in their orientation preference before V1. Additional experiments will be performed to determine whether the early matching in the dLGN is experience-dependent by recording from mice reared in complete darkness from birth. Finally, by combining cortical silencing and in vivo whole cell recording, the investigators will examine whether the binocular responses of dLGN input determine the binocular tuning of individual V1 neurons. Together, these experiments will reveal a novel link between the developmental plasticity at two successive stages of visual processing, and determine the role of visual thalamus in guiding binocular development in V1. Because ocular dominance plasticity and its critical period is a model for amblyopia and strabismus, a full understanding of cortical and subcortical changes that normally take place during development will have profound implications for the understanding and treatment of these diseases.