Anatomical and functional organization of inter-areal feedback circuits in the visual cortex, and their impact on neuronal responses - In the mammalian sensory cortex, hierarchically-organized areas are reciprocally connected via feedforward (FF) and feedback (FB) circuits. FF connections generate the more complex response properties of neurons in higher areas within parallel streams specialized in processing specific stimulus attributes. In contrast, the function of FB connections remains unknown. In the visual cortex, FB has been implicated in top-down phenomena, such as visual attention, prediction, and visual context. However, these roles have remained hypothetical, due to the lack of tools to selectively label, record, and manipulate the activity of FB neurons. As FB circuits are ubiquitous in cortex, and abnormalities in FB connectivity and function in humans have been linked to neurological disorders, such as attention deficits and autism, it is important to understand normal FB connectivity and function in primates. During prior funding, we developed novel viral and optogenetic tools to selectively label FB neurons, trace their inputs and outputs, and record and manipulate their activity in primate cortex. Using these tools, we found that, anatomically, FB connections between visual areas V2 and V1 form parallel pathways, make direct contacts with V1 neurons sending FF projections to V2, and link V2 and V1 neurons preferring similar visual stimulus features. Functionally, we found V2 FB conveys global visuo-spatial information to V1, and controls the receptive field size, surround suppression and response amplitude of V1 cells. In these studies, however, we did not disentangle FB connections related to different layers. Anatomical, functional and theoretical evidence indicates that within each parallel FB pathway there are at least two, and probably more, sets of FB arising from, and terminating in, different layers, likely having distinct organizations and functions. Our goal is to understand the connectivity and computational function of FB connections related to different layers of origin and termination within each FB stream. Using selective labeling of FB neurons, we will determine the differential contribution of FB from different V2 layers to their V1 termination layers. Moreover, using rabies-virus-mediated monosynaptic input tracing (TRIO) combined with optical imaging of V1 and V2 functional maps, we will determine the functional connectivity of, and the V1 cell types targeted by, different laminar-specific FB sets (Aims1,2). Finally, we will optogenetically manipulate the activity of distinct V2 FB sets to determine their differential impact on V1 neurons' spontaneous and visually-evoked responses (Aim3). Impact. This proposal will reveal the anatomy and function of laminar-specific FB circuits between V2 and V1. This information will inform and refine models of FB function, influence the design of artificial systems striving to achieve vision, and provide new insights into the circuit-level bases for neurological disorders that have been linked to abnormal FB connectivity and function (attention disorders, autism).
