Dissection of Neuronal Circuits Underlying Obesity

Rockefeller University, New York NY

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Abstract

DESCRIPTION (provided by applicant): The prevalence of obesity is continuing to grow in our nation. Obesity is associated with many diseases and thus represents a pressing medical and public health concern. The goal of this proposal is to understand the neuronal circuits that respond to feeding. The proposed aims will be addressed by utilizing a neuronal tracing system, which employs the Pseudorabies virus (PRV) recombinant. A PRV, which is conditional for Cre-expression in leptin receptor or NPY positive neurons, will be used to infect mice. Cells with direct and indirect projections in these neurons will be visualized by the expression of GFP. In this application, this novel methodology will be used to characterize efferent signaling from feeding centers of the brain as well as the integration of afferent neuronal inputs from peripheral sites involved in feeding behavior. A method will be developed which will allow the recovery of cellular RNA from the labeled cells in these neural networks. Whether changes in plasma leptin result in alteration of the architecture and gene expression in these circuits will be examined as well.