The interaction of cortical and subcortical processing in natural sensory behavior - Abstract Our brains have evolved to extract relevant sensory information from rich and complex natural environments in order to drive appropriate behavior. Multiple brain structures can play a role in such processing, and while cortex is often most prominent in mammalian studies, many behaviors can also be mediated by superior colliculus, particular orienting and avoidance responses to salient stimuli. However, the relative roles of cortex and superior colliculus, and the interactions between them, are poorly understood as the two are not typically studied together, particularly within a natural behavior context. Here we will use prey capture in the mouse as an ethological paradigm to study the computations performed by cortex, and their impact on SC, across two sensory modalities - visual and auditory. Based on our preliminary data, we hypothesize that cortex is necessary under conditions that require flexible identification of stimuli in complex sensory environments, whereas SC serves as a specific feature detector in simple conditions. We further hypothesize that in both cases, SC serves as the effector to orient towards prey, with cortex mediating its role in complex environments via top-down modulation of SC. In order to test potential mechanisms, we will first determine the role of cortex in different aspects of sensory processing, by inactivating primary sensory cortex (V1 or A1) during prey capture, under conditions where we vary the task complexity from isolated stimuli to complex sensory environments. We will next determine the information encoded in cortex and SC during these different conditions via extracellular multisite recordings during both prey capture behavior and head-fixed passive presentation of stimuli. Finally, we will determine the interaction between cortex and SC by measuring the impact of inactivating cortico-collicular projections on neural coding in SC. All these experiments will be performed in both visual and auditory domains in order to determine shared principles that may serve as canonical computations in the cortico-collicular system. Furthermore, this project builds on the complementary expertise in these domains of co-PIs Niell (visual physiology) and Wehr (auditory physiology), who have an established history of collaboration including developing the prey capture paradigm previously.