CNS MELATONIN TARGETS AND PHOTOPERIOD-INDUCED OBESITY

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The purpose of this grant proposal is to develop novel paradigms, acquire new techniques and apply them to either extensions of current research themes or to new research endeavors related to these themes in order to develop further the career of the PI. Three Specific Aims are proposed, each with a set of experiments. Specific Aim I: What is the role of the innervation of adipose tissue in the photoperiodic control of seasonal obesity? Experiments are proposed to extend our recent report of the direct innervation of white adipose tissue (WAT) by the sympathetic nervous system (SNS) and our finding of sensory innervation of WAT (see Preliminary Studies), and the role of each in the photoperiodic control of seasonal obesity in Siberian hamsters. Four questions will be answered: 1) Can the short day-induced decreases in body fat occur independently of the SNS innervation of WAT?, 2) Does the relatively separate SNS innervation of WAT converge in the CNS?, 3) What is the extent of the sensory innervation of WAT?, and 4) What is the functional role of the sensory innervation of WAT in the short day-induced decreases in body fat? Specific Aim II: What is the relationship between the amount of total body fat and level of food hoarding and what role does the sensory innervation of adlpose tissue play in this relationship? Siberian hamsters appear to respond to decreases in body fat by increasing externally stored energy in the form of a food hoard. Naturally occurring and experimentally induced decreases in body fat will be used to test further the inverse relationship between total body fat and the level of food hoarding in Siberian hamsters, and the role of the sensory innervation of WAT in this relationship. Food hoarding will be studied using a simulated burrow system. Three questions will be answered: 1) Do the short day-induced decreases in body fat stimulate food hoarding?, 2) Does partial surgical lipectomy (fat removal) stimulate food hoarding?, and 3)What is the role of the sensory innervation of WAT on the short day-induced increases in food hoarding? Specific Aim III: Can c-Fos activity be used to identify the functional sites of reception/transmission of melatonin signals and thefr efferent projection fields? Experiments are proposed to test the hypothesis that stimulation of the putative sites for the reception/transmission of melatonin signals activates the immediate-early gene c-Fos. This will be accomplished by using the timed infision paradigm for the subcutaneous or intracerebral programmed delivery of physiologically relevant melatonin signals to pinealectomized Siberian hamsters. Three questions will be answered: 1)Do systemic infusions of melatonin activate neurons in the three brain sites that show melatonin binding in Siberian hamsters and what are the neurotransmitter phenotypes of these cells?, 2) Where are the efferent projection fields of the cells that are activated by melatonin and located in the three brain sites that show melatonin binding?, and 3) Can these putative efferent projection fields be verified using retrograde tract tracing combined with c-Fos immunocytochemical techniques?