PIVOTAL ROLE OF ENERGY METABOLISM IN CONTROL OF BEHAVIOR

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This application for an NIMH Research Scientist Development Award is focused on the sensory and neuroendocrine mechanisms that change reproductive physiology and behavior when females are faced with energetic challenges (such as food shortages or increased exercise requirements). This work is relevant to a number of health issues. Specifically, the work has implications for understanding infertility associated with excessive body weight loss and gain, and with diseases that affect caloric homeostasis, such as diabetes and hypoglycemia. More generally, this work will elucidate the interaction between metabolism and the nervous system and the links among nutrition, exercise, energy metabolism, and mental health. The work is focused on female rodents because they are exquisitely sensitive to changes in energy supply and demand. For example, when they experience prolonged food shortages or decreases in ambient temperature they will change their food preferences and foraging strategies, build larger nests, attenuate or suspend reproductive effort, or in extremes, enter a bout of hibernation. These responses may all be viewed as adaptations to changing energy requirements. The central theme is the pivotal role of sensory detectors of metabolic energy availability. The applicant has shown that anestrus, nest building, and hibernation can be initiated by treatments that block the cellular availability, and hence oxidation, of specific metabolic substrates. Her future work will revolve around the nature and location (anatomical sites) of sensory detectors of metabolic fuel availability and the interface of these detectors with neuroendocrine systems controlling estrous cycles, food intake, and thermoregulatory behaviors. She will study the effects of metabolic challenges on these behaviors using intracerebral microinjections, lesions of specific brain stem nuclei, tract-tracing and c-fos immunocytochemistry.