7. PROJECT SUMMARY/ABSTRACT Over the past 30 years, the obesity epidemic has grown such that more than 2 in 3 adults are classified as overweight or obese, and about 1 in 6 children and adolescents are considered to have obesity 1,7. The alarming increase in the prevalence of obesity is in large part due to the increasing size and number of meals that people consume 33,34, which are often influenced by learned experiences and environmental food- associated cues that can drive an individual to eat beyond metabolic/energy need 10,11. Recent publications from our lab4,5 indicate an important role for ventral hippocampus (CA1v) projections to the lateral hypothalamic area (LHA) and medial prefrontal cortex (mPFC) in mediating conditioned and motivated aspects of feeding behavior. However, CA1v neural pathways and behavioral mechanisms for the integration of food-related internal and environmental cues are not fully characterized. The goals of this proposal are to [1] map primary 1st-order projections of CA1v neurons, [2] identify collateral pathways branching from CA1v>mPFC and CA1v>LHA pathways, and [3] determine 2nd-order projection outputs of CA1v>mPFC and CA1v>LHA pathways (Aim I). This proposal also aims to test the functional relevance of CA1v>mPFC and CA1v>LHA pathways to higher-order aspects of feeding by combining viral-mediated disconnection of CA1v pathways with rodent feeding-relevant behavior paradigms that probe memory processes related to internal and external feeding-relevant cues (Aim II). Overall proposed experiments assess multiple levels of analyses and utilize state-of-the-art methodologies, including conditional virogenetic neural pathway tracing and functional chemogenetic methods to unravel the neural circuits that connect learning and memory with feeding behavior.

8. PROJECT NARRATIVE The number of overweight and obese individuals has rapidly increased in the past thirty years in the United States, thereby raising public health concerns. An understanding of the neurobiological mechanisms that drive excess eating are necessary for the development of more effective behavioral and pharmacological therapies. The proposed experiments investigate a novel role of the ventral hippocampus, a brain region classically associated with memory function, in the control of excessive feeding behavior that is triggered by environmental food-related cues.