SUMMARY The brain transforms raw sensory input into perception and cognition, and this transformation relies on computations performed across neuronal circuits. Fortunately, the anatomy of cortical microcircuits in non- human primate models is much better understood today than decades ago. Indeed, sensory information travels in the cerebral cortex along feedforward and feedback pathways. While bottom-up feedforward connections have been extensively examined over the past several decades, the functional role of feedback projections continues to remain mysterious. Cortical feedback has been previously examined by reversibly inactivating higher cortex using a variety of methods, and measuring effects in single neurons in lower cortex. While important, previous studies modulating cortical feedback using techniques such as pharmacological inactivation, cortical cooling, electrical microstimulation, or transcranial magnetic stimulation, suffer from several key limitations, including poor spatial localization and temporal precision, and exclusive focus on single neuron responses. To overcome these limitations we will use optogenetic and multi-electrode electrophysiological methods in non-human primates to inactivate cortical feedback in real time based on cell localization, laminar location, and connectivity, and examine its impact of neural coding and behavior. To this end, we have chosen a major visual pathway involving primary visual cortex (V1) and mid-level visual cortex (V4). V4 neurons are believed to relay top-down signals related to behavioral context and attention to area V1 via direct feedback projections. Our working hypothesis is that feedback connections exhibit functional specificity and increase the population coding accuracy and communication among cortical neurons to improve behavioral performance. Our proposal will test the feasibility and validate the use of optogenetic methods in conjunction with multi-electrode recordings of population activity to directly address several of the desired capabilities for the next generation of neuroscience tools in non-human primates. We propose a new way to optogenetically control cortical feedback which will lay the groundwork for an interrogation of large-scale circuits at an unprecedented level of resolution. Thus, our proposal represents a significant step toward mapping the dynamic activity of relevant brain circuits in real time and understanding their impact on network coding and behavioral decisions.

PROJECT NARRATIVE We propose to causally manipulate an important type of brain connectivity, feedback projections, believed to play a major role in attention, expectation, and decision making. To accomplish this goal, we plan to shine light at different depths (layers) inside the brain to control the responses of neurons while animals perform a behavioral task. These efforts can offer new insights into a network-based understanding of perceptual decisions, and help improve future visual prosthetic devices that would take into account feedback projections, which are a general type of connectivity found in the brain of all mammalian species.