PROJECT SUMMARY / ABSTRACT Understanding how the brain makes decisions based on noisy sensory information is one of the central goals of neuroscience, but past efforts to study this process have been hindered by three challenges: (1) Animals make decisions in complex environments that do not always map onto the simplistic binary decision tasks typically used in the lab; (2) Decisions are influenced by slowly changing variables like environment value that are difficult to study in short experiments; (3) Decision making involves a large network of interacting brain regions, each of which influences and is influenced by many others. The proposed research addresses these three problems simultaneously by developing a complex yet naturalistic foraging task for mice and applying recently developed neurobiological techniques to record and manipulate neural activity in multiple brain regions over long time scales. The long-term objective is to use this combination of behavioral and neurobiological techniques to understand decision making in a naturalistic foraging context. The proposed research investigates the hypothesis that foraging decisions are driven by neural integrator mechanisms akin to those used to integrate sensory evidence for perceptual judgments, and require bidirectional communication between cortex and striatum, which are often studied in isolation but in fact must communicate to generate decisions. Simultaneous optogenetic perturbations and large-scale recordings will be used to dissect the interplay between medial prefrontal cortex (mPFC) and dorsomedial striatum (DMS), which of the many interconnected regions of cortex and striatum are among the most likely to contribute to the integration processes needed to forage efficiently. Indeed, preliminary mPFC recordings show signatures of temporal reward integration. Spatiotemporally precise optogenetic perturbations with simultaneous neural recordings will reveal which aspects of this computation occur locally in mPFC and/or through corticostriatal interactions. Finally, novel longitudinal electrophysiological recording techniques will answer how environment value, a key variable in foraging decisions, is tracked over long time scales (days). This question has been difficult to study in the past due to the technical challenge of tracking the same neurons over time scales longer than several hours. Together, these experiments will advance the field’s understanding of how distributed networks of brain areas solve a complex yet ethologically relevant decision-making problem. This will create deeper knowledge of how the healthy brain tracks rewarding outcomes to make decisions, which is critical for understanding what goes awry in dysfunctional states like addiction, obsessive compulsive disorder, and mood disorders. This project will take place in the Uchida Laboratory in the Department of Molecular and Cellular Biology at Harvard University. The Laboratory and Department are well-equipped to ...