Evidence supports a crosstalk between anxiety, emotion and metabolic disease; however, the neural circuits and molecular mechanisms that underlie anxiety and its connection to metabolism are not clear. The lateral hypothalamus (LHA) is a brain region well known for its role in feeding and metabolism, and recent evidence links LHA neurons to classic anxiety circuits. Our new data demonstrates a strong role for a unique population of galanin-expressing (LHA) neurons as modulators of anxiety behavior. We have also previously shown these neurons to drive food reward behaviors. Thus, LHA galanin neurons may provide a crucial link between feeding behavior, metabolism, and emotional status. The goal of this project is to extend the functional LHA galanin circuit by defining the neural circuit inputs and outputs and molecular mechanisms that orchestrate the role of these neurons in anxiety and stress behaviors. We will accomplish this goal through identification of the components of the LHA galanin circuit that are required for regulation of anxiety and testing the dependence of this effect on intact galanin signaling, investigating alternative gene products which may regulate anxiety via LHA galanin neurons, and finally, determine if LHA galanin neurons are targets of the higher order anxiety circuit. The results from this project will reveal mechanisms by which discrete brain regions such as the LHA may influence both emotion and metabolism, providing crucial insight into how dysregulation of emotion and metabolism may interact.
The lateral hypothalamus (LHA) is a brain region well known to influence feeding behavior and metabolism; however, recent studies support a role for the LHA in emotional behaviors such as anxiety and stress. Our lab recently discovered that a specific population of neurons in the LHA that express the neuropeptide galanin are strong modulators of anxiety and stress-related behaviors. When these neurons are activated synthetically in the mouse, anxiety-like behaviors drastically decrease while the intake of rewarding foods increases. This suggests that the LHA could be an interface for the association of feeding behaviors with emotional status. This project seeks to determine what other regions of the brain cooperate with the LHA galanin neurons to modulate anxiety and stress behavior and define the molecular mechanisms through which these behaviors are modified. We expect that this project will reveal new mechanisms by which the influence of emotion on metabolic status may be integrated by the brain.
