Neural Mechanisms of Prefrontal Influence on Food Intake

Yale University, New Haven CT

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Abstract

DESCRIPTION (provided by applicant): Obesity has significant consequences in terms of medical cost and quality of life. Eating and body weight are both genetically influenced while also clearly sensitive to the food environment. It is clear that our inability to control intake of readily available food is central to this problem. In essence, this is similar to drug addiction where people want to control a behavior, but struggle to do so. Human imaging data implicates regions of the cortex in this type of self-regulation and decision-making. Studies in animal models of addiction support an important role for prefrontal cortex (PFC) in craving and intake. However, most studies of feeding in animal models have not included the cortex, with prominent models primarily focused on hypothalamic circuits. This proposal aims to fill in this gap by incorporating the PFC into our views and models of intake control. Preliminary data establish that optogenetic stimulation of dopamine receptor type 1 (D1) pyramidal neurons of the PFC is sufficient to increase food intake. Additional circuit analysis identifies the basolateral amygdala (BLA) as a potential target region mediating these effects. The proposed work will interrogate this novel D1 PFC to amygdala circuit while also connecting it with other brain regions that are known to influence feeding. This work is important, as it will expand our neural models of feeding and begin to bridge the gap between rodent and human studies.