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Physiology of Raphe Magnus Cells During Wake and Sleep

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A core issue in biology is to explain how an action pattern is selected and completed in the presence of conflicting goals. This proposal tests the novel hypotheses that the medullary raphe magnus (RM) defends food consumption from distraction and therefore contributes to obesity but that this function is not engaged during illness or nausea when anorexia occurs. Feeding and reactions to moderately noxious stimuli are well matched in terms of importance to survival and urgency and are both experimentally tractable. We previously showed that withdrawals from noxious heat are suppressed during feeding in rats and that RM cells are required for this suppression. This project aims to further investigate this phenomenon in healthy and ill rats fed ad libitum. To test whether rats need to self-initiate feeding in order to trigger RM pain suppression, Aim 1 will compare the reactions to noxious heat during quiet wake and ingestion of intraorally infused substances. This aim will also test how hunger, nutritional content, palatability, and orolingual movements influence the suppression of pain reactions during food consumption. RM cells will be recorded in awake, behaving rats to determine whether pain-inhibitory OFF cells are excited and pain- facilitatory ON cells inhibited during consumption of oral infusates. Experiments added in this revision will test how increasing the intensity and duration of the pain stimulus or decreasing the salience of the food modifies the suppression of pain reactions as well as RM cell activity during feeding. Preliminary results suggest that RM mediates withdrawal suppression during ingestion of sucrose, water or saccharin, independent of hunger or nutritional value, but that withdrawals are not suppressed during infusion of quinine. Aim 2 will determine whether RM's defense of feeding is turned off by nausea, illness, or cues associated with illness. Preliminary data suggest that withdrawal suppression does not accompany ingestion when the animal is ill or nauseated or in the presence of illness-associated cues, suggesting that changes in RM cell discharge that normally accompany food consumption do not occur under these health conditions. Linking sensory modulation to the competitive salience of feeding under different health conditions (well-being, illness) allows appropriate adjustments to attend complex behaviors and may serve as a model of how the brain determines priorities between competing motivations and actions.

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