DOI: 10.25549/usctheses-c40-380061
title: The bi-directional control of feeding behaviors through endocrine-hippocampal neural circuits

description: Since the 1980s, obesity prevalence in the United States has risen at an alarming rate where excessive food intake represents a phenomenon that is in large part driving today’s obesity epidemic. In light of this, current research has focused on the physiological and neurobiological mechanisms that underlies the types of behaviors that can trigger excessive feeding. While historical feeding research has focused on hypothalamic and hindbrain nuclei that mediate feeding in response to metabolic deficits, the complexities of feeding behaviors have shifted the field towards examining “higher-order” brain regions that regulate learning, memory, and reward. Given the importance of learned aspects of feeding behavior that can trigger excess food intake, the research presented in this dissertation places a strong emphasis on the hippocampus, a brain region traditionally associated with mnemonic functions. Importantly, recent investigations have now revealed key roles for the ventral subregion of the hippocampus (vHP) in the control of food intake and energy balance, where integration with peripherally or centrally derived feeding relevant signals (e.g. leptin, ghrelin, GLP-1) reflect a potential neurobiological mechanism that underlies vHP mediated learned feeding behaviors. Thus, the data presented in this dissertation delineate the neuroanatomical, neurobiological and behavioral mechanisms through which these endocrine feeding-relevant signals in the vHP control feeding behaviors and energy balance. We first focus on an orexigenic (food intake stimulatory) stomach-derived feeding signal, ghrelin, where multiple levels of analyses are utilized to 1) determine the importance of vHP ghrelin signaling on learned feeding behaviors, 2) investigate the downstream neural targets and pathways that modulate vHP ghrelin mediated feeding, and 3) unravel the types of learned feeding behaviors that engage the vHP ghrelin system. Next, we hone in on an anorexigenic (food intake inhibitory) feeding signal, glucagon-like peptide-1 (GLP-1; produced in the distal small intestines and hindbrain), and utilize parallel and developing strategies to determine 1) the role of vHP GLP-1 receptor (GLP-1R) signaling in feeding behaviors, 2) identify key downstream neural targets and pathways that regulate vHP GLP-1R-mediated feeding behaviors, and 3) identify the behavioral mechanisms through which vHP GLP-1R signaling reduces feeding behaviors. Overall, we reveal that hippocampal-endocrine signaling is a critical neurobiological substrate that regulates both anorexigenic and orexigenic feeding behaviors (i.e. bi-directional control of food intake through hippocampal processes), particularly those involving interactions between learning and memory processes and food-related cues. These findings illuminate the importance of the higher-order brain substrates to food intake control and reveal novel neural pathways through which we can further understand the neurobiological mechanisms of feeding behaviors that are driving today’s obesity epidemic.