Deciphering a hippocampus to hypothalamus feeding circuit via the septal nucleus.

Abstract

The neural circuits controlling feeding are concentrated in the hypothalamus and hindbrain. These circuits primarily control homeostatic feeding behavior, which can be broadly defined as increasing feeding in response to hunger or decreasing feeding in response to satiety. However, non-homeostatic factors, such as the emotional state of an animal, can also profoundly affect feeding behavior. Therefore, the current thesis project sought to determine how primary emotion centers in the brain influence the known homeostatic feeding circuitry in the hypothalamus. In particular, given that ventral hippocampus (vHPC) and septum are involved in emotional processes, influence feeding behavior, and are anatomically connected to hypothalamic feeding circuitry, this dissertation aimed to determine the cell-types in vHPC and septum that control feeding and to functionally connect these cell-types to the primary feeding circuitry located in the hypothalamus. To accomplish these central aims, chemogenetic and optogenetic approaches were utilized to selectively manipulate neural activity within distinct ventral hippocampal and septal cell types and neural circuits. These approaches were complemented by traditional anterograde and retrograde tracing techniques and chemo/optogenetic circuit mapping approaches to define the neural circuits responsible for vHPC and septal control of feeding behavior. We find that chemogenetic activation of ventral hippocampal glutamate neurons reduces feeding, while inhibition facilitates feeding. We further dissect a functional neural circuit pathway from ventral hippocampus to lateral septum that is sufficient to suppress feeding behavior. Within the septum, both chemo/optogenetic activation of septal GABAergic neurons reduces feeding, while inhibition of these neurons increases food intake. Utilizing optogenetic circuit manipulation approaches, we demonstrate that septal GABAergic neurons reduce feeding, at least in part, by projecting to hyperphagia-inducing GABAergic neurons located within the lateral hypothalamus. Taken together, our findings expand upon the known roles for ventral hippocampus and septum in energy homeostasis by providing the specific cell-types and neural circuits governing vHPC and septal control of feeding behavior. Given the role for ventral hippocampus and septum in emotional processes and energy homeostasis, we propose that the described vHPC and septal circuits represent promising neural circuits for investigating interactions between feeding, emotional state, and motivated behavior.