BRAIN Initiative K99 Project

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Food consumption is fundamental to species survival and understanding the neuronal circuitry underlying feeding behaviors is of the utmost importance. Amassing evidence supports the idea that control of caloric intake is complex and involves calculations of hedonic value, reward and motivation. Thus, it requires interactions between brain regions classically implemented in feeding (such as the lateral hypothalamus; LH) and the regions modulating reward (such as the ventral striatum). While the intersection of these regions has been suggested, the cell-type specific circuitry linking these pathways is poorly understood. The objective of this proposal is to further elucidate the cell-type specific circuitry underlying striatal-to-lateral hypothalamic connections and determine its role in feeding, while gaining training in new neuronal circuitry mapping techniques. There is evidence that the striatum exerts its control over feeding behaviors by interfacing with the LH. Previous research indicates that the ventral striatum, and specifically the nucleus accumbens shell (NAcS), and the LH are connected via a direct pathway. However, rudimentary tracing and behavioral studies have suggested a second, indirect pathway, with the NAcS projecting to the ventral pallidum (VP), which in turn projects to the LH. However, despite this initial evidence, cell-type specific, neuronal circuitry in this indirect pathway remains unknown. Using viral tracing methods and chemogenetic approaches I will determine the cell-types implicated in each component of this three-part circuitry, and how they mediate feeding behaviors. I hypothesize that GABAergic striatal projection neurons expressing the dopamine D2 receptor in the NAcS preferentially innervate GABAergic cells in the VP, which in turn disinhibit LH GABA neurons to facilitate feeding. Furthermore, in understanding the brain pathways and connectivity underlying food intake behaviors, this project will ultimately allow us to better understand perturbations that occur in disease states such as obesity.