Food intake control by leptin signaling in the hippocampus

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DESCRIPTION (provided by applicant):This proposal describes a 3-year training program designed to provide the candidate (Dr. Scott E. Kanoski) with the expertise needed to incorporate a range of neuroanatomical, molecular, and other career oriented skills (e.g., mentoring, lab management, grant writing) that will broaden the scope of his obesity-focused research career. The proposed training plan will substantially benefit the candidate's ability to establish and maintain a productive independent behavioral neuroscience laboratory at the University of Southern California (USC) conducting research focused on obesity treatment and prevention. The candidate received a Ph.D. in Aug. 2009 and conducted research as a postdoctoral fellow in the Department of Psychology at the University of Pennsylvania. His position as Assistant Professor of Biology at USC begins January 2013. The Department of Biology at USC has a strong research tradition that will provide an ideal training and research environment for the candidate. The primary mentor, Dr. Alan Watts, Professor of Biology at USC, is a well-established researcher in the field of behavioral neuroscience and an expert in the neuroanatomical and neurochemical systems that control energy balance and metabolism. To facilitate the novel interdisciplinary approaches of the proposed research, the candidate will also be guided by co-mentor, Dr. David McKemy (USC), a prominent neurobiological researcher in the fields of somatosensation and nociception, and by Dr. Harvey Grill (University of Pennsylvania), a renowned expert in the neuroendocrine controls of feeding and energy expenditure. The research in this proposal will examine the novel hypothesis that the adipose cell-derived hormone leptin signals in the ventral hippocampus (VHPC), a brain region that regulates learning and motivational processes, to suppress motivational behaviors related to obtaining rewarding, palatable foods. The experiments described in the proposal use a rat model and integrate state-of-the-art neuroanatomical (immunohistochemistry and neurological tracers), molecular (immunoblot, qPCR), genetic (RNA interference), pharmacological (central delivery of agents), and behavioral techniques (learning and memory paradigms). Building directly on preliminary data presented in this proposal, experiments are designed to: 1) assess whether leptin receptor (LepRb) signaling in the VHPC is physiologically relevant to learned motivated behaviors directed towards food procurement, 2) identify the neural circuits that communicate in concert with the VHPC to reduce food intake via leptin signaling, and 3) identify whether food intake reduction by VHPC leptin involves brain-derived neurotrophic factor (BDNF) signaling. Results will contribute to the development of pharmacological obesity treatment by informing about the neuroendocrine and intracellular/molecular systems that control food intake and food-motivated behavior.