The functional role of frontal and parietal feedback to visual cortex in selective visual attention - PROJECT SUMMARY: Imagine Times Square in New York City: tall buildings, flashing lights, a swarm of people. This visual scene represents a potential overload of sensory information. To guide behavior, the brain uses a collection of filtering mechanisms that either boosts the processing of behaviorally relevant information or suppresses the processing of distracting information. Impairments in this selective processing of sensory information can have critical consequences for human health. Such consequences are apparent, for example, in visuo-hemineglect associated with stroke, and in some neurodevelopmental disorders, such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). The present proposal specifically focuses on the selective processing of locations in visual space, referred to as spatial attention. A large-scale network of brain regions directs spatial attention, but the specific contributions of each network node to attention-related enhancement and suppression remain largely unknown. Here, we will test whether distinct circuits within the attention network are driving these complementary processes in a well-characterized region of visual cortex, i.e., visual area 4 (i.e., V4). We will specifically investigate functional contributions from two cortical nodes of the attention network in macaques: the frontal eye fields (FEF) in frontal cortex and the lateral intraparietal area (LIP) in parietal cortex. FEF and LIP both contribute to top-down attentional control, based on behavioral goals. To determine whether there are distinct or redundant neural circuits underlying the effects of attention-related enhancement and suppression on visual processing, we will record layer-specific neural activity from V4, while simultaneously using optogenetics (i.e., the use of genetically coded, light-driven ion channels or pumps) to inactivate known corticocortical pathways, either from FEF to V4 or from LIP to V4. The use of optogenetics, in comparison to other causal manipulations (e.g., electrical microstimulation or pharmacological inactivations), will allow us (i) to isolate contributions from specific between-region, corticocortical pathways and (ii) to compare the effects of inactivating these pathways, from either FEF or LIP, on different trials within the same experimental session. The present proposal has three specific aims: (i) to establish the retrograde-only expression of virus in FEF and LIP after optogenetic injections in V4, (ii) to test whether corticocortical pathways from FEF and LIP make distinct contributions to attention-related neural effects in V4, and (iii) to test whether the complementary processes of attention-related enhancement and suppression interact in V4. We will test the Central Hypothesis that FEF primarily contributes to the goal- directed enhancement of behaviorally relevant information in V4 through connectivity in supragranular layers, while (ii) LIP primarily contributes to the goal-directed suppression of distracting information in V4 through connectivity in infragranular layers. The present proposal will advance our overarching objective of understanding how the attention network shapes visual processing of our complex and dynamic environment.