Research into the location and operating characteristics of the neural substrates that control feeding behavior and energy expenditure is essential for an understanding of the basic physiology of intake control, and an appreciation of the CNS underpinnings of and treatments for obesity, anorexia, cachexia and other feeding pathologies. The field has been profoundly energized by a number of findings that have emerged in the past few years - from the discovery of leptin, and its central receptors to the identification of a variety of important neuropeptide mediators and their interactions. The findings have been cast firmly from a hypothalamic perspective, emphasizing leptin action on arcuate nucleus and in particular on those neurons with POMC and with NPY phenotype. It has become clear, however, that virtually all of the relevant control elements (e.g., leptin receptors, relevant neuropeptide receptors and cell bodies) are re-represented in the caudal brainstem. We propose to explore the contributions of brainstem substrates to the control of food intake and energy expenditure, with a focus on the performance of the chronic decerebrate rat (CD) relative to its neurologically intact control. Demonstrated competencies of the CD reflect the functional operation of circuits intrinsic to the brainstem. The principle measures include intake responses, core and brown-fat temperature, oxygen consumption, respiratory quotient, and heart rate. The responses are measured as functions of: (a) food deprivation and overfeeding, and (b) delivery of leptin and ghrelin, and neuropeptide (NPY, CRF, GLP1, melanocortin) receptor agonists and antagonists. In addition, changes in POMC and NPY mRNA expression in brainstem neurons is evaluated as a function of deprivation and leptin treatment. The proposed experiments should provide essential information about energy balance control functions that are endemic to the brainstem, and those functions that are served by an interaction between brainstem and hypothalamic structures.
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