Project Summary Adolescence is an important period for neural and cognitive development. Many perceptual and cognitive abilities rely on inputs from higher cortical regions, which are known to develop well into early adulthood, sending feedback in a top-down manner to lower sensory regions, such as primary visual cortex (V1). How these feedback projections develop during adolescence is poorly understood. Moreover, the adolescent development of top-down projections to V1 may have important implications for higher order visual processing, which is disrupted in a number of neurological and neuropsychiatric disorders. This project investigates the development of top-down inputs to V1 during adolescence in a mouse model, focusing on projections from the anterior cingulate area (ACa; a region of mouse prefrontal cortex) through the lens of visual context processing, a complex form of visual processing dependent on cortical feedback. We hypothesize that ACa input to V1 becomes increasingly refined during adolescence, permitting the maturation of visual context processing. The specific aims of this project are (i) to characterize ACa innervation of V1 across adolescence, both structurally and functionally, and (ii) to investigate a role for ACa-V1 circuit development in visual context processing. Aim 1 will characterize the structural development of ACa axons and synapses in V1 (Aim 1.1) and the activity of these inputs in V1 during contextually varied visual stimuli across adolescence (Aim 1.2), using confocal and two-photon microscopy, respectively. Aim 2 will employ a chronic chemogenetic approach to test the necessity of ACa feedback to V1 specifically in the adolescent phase for the emergence of mature neural circuitry and visual context processing. Through this project, we seek to generate novel insight into the development of top-down cortical circuits for visual processing and how this period of circuit development may be a susceptible window during which disrupted visual processing emerges in neurological and neuropsychiatric disorders. To achieve these goals, the candidate will receive training from a skilled team of technical and scientific advisors; specifically, the candidate will gain insight from the sponsor’s technical experience with two-photon imaging, electrophysiology, and circuit analysis in the field of visual systems neuroscience, the senior co-sponsor’s developmental and stereological expertise, and a collaborator’s confocal and synaptic quantification knowledge. Georgia State University provides a well- equipped and collaborative environment in which to conduct this research. Training will be enhanced by intramural and extramural opportunities for science education, mentorship, and advocacy.