Voluntary exercise modulation of olfactory function

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ABSTRACT Previous efforts in our lab have uncovered that consumption of a fatty diet leads to a reduction in the number of olfactory sensory neurons in mice. Voluntary exercise has been shown to protect neurons in several brain areas from different types of injuries. The primary objective of this project is to determine if participation in voluntary exercise is capable of protecting the neurons of the olfactory system from the detrimental effects of a fatty diet. Beyond protection, I also intend to determine if the well-established neuromodulatory effects of voluntary exercise extend to the olfactory system. The evidence that associates olfactory disorders with neurodegenerative disorders, such as Alzheimer’s, continues to grow and for this reason it is important to investigate the effects of both diet and exercise on this oft-ignored sensory system. These studies will be accomplished through modification of diet composition to induce obesity, application of pair-feeding to manipulate body weight gain, provision of a home cage running wheel, histological analyses to determine anatomical changes, and electrophysiological analyses to assess changes in cellular biophysical properties. The basis of these experiments is the hypothesis that a fatty diet creates an inflammatory environment that damages the olfactory system of mice and voluntary exercise is a neuromodulator of the olfactory system that will prevent this damage if the mice are allowed to participate in such exercise while they subsist on a fatty diet. The specific aims designed to investigate this hypothesis are 1) To determine if ingestion of a fatty diet without overconsumption, and therefore without the concomitant weight gain, is sufficient to decrease olfactory sensory neuron abundance and their correlate axonal projections. 2) To determine if voluntary exercise is capable of preventing and/or abrogating the structural loss in the olfactory epithelium and olfactory bulb that is caused by consumption of a fatty diet. 3) – To determine if voluntary exercise ameliorates the loss of insulin modulation in mice challenged with a fatty diet. Electrophysiological properties of the olfactory bulb primary neurons will be determined and compared.