Physiology of Raphe Magnus Cells During Wake and Sleep

描述（由申请人提供）：生物学的一个核心问题是解释在存在冲突目标的情况下如何选择和完成行动模式。这一提议验证了一种新的假设，即中缝大髓质（RM）保护食物摄入不受干扰，从而导致肥胖，但当厌食症发生时，这种功能在疾病或恶心期间不参与。就生存的重要性和紧迫性而言，进食和对中度有害刺激的反应是很好的匹配，并且在实验上都是可处理的。我们之前的研究表明，在大鼠的喂养过程中，对有害热量的提取受到抑制，并且这种抑制需要RM细胞。本项目旨在进一步研究自由喂养的健康和患病大鼠的这一现象。为了测试大鼠是否需要自我启动进食来触发RM疼痛抑制，Aim 1将比较静醒时对有害热量的反应和口服输注物质的反应。这个目标还将测试饥饿、营养成分、适口性和多语运动如何影响食物消耗过程中疼痛反应的抑制。将在清醒、行为正常的大鼠中记录RM细胞，以确定口服输注时疼痛抑制性OFF细胞是否被兴奋，疼痛促进性ON细胞是否被抑制。本修订版中增加的实验将测试增加疼痛刺激的强度和持续时间或减少食物的显著性如何改变对疼痛反应的抑制以及喂食期间RM细胞的活性。初步结果表明，RM在摄入蔗糖、水或糖蛋白时介导戒断抑制，与饥饿或营养价值无关，但在输注奎宁时不抑制戒断。目的2将确定RM对喂食的防御是否被恶心、疾病或与疾病相关的线索关闭。初步数据表明，当动物生病或恶心或存在疾病相关线索时，戒断抑制不会伴随进食，这表明在这些健康条件下，通常伴随食物摄入的RM细胞放电变化不会发生。将感觉调节与不同健康状况（健康、疾病）下进食的竞争性显著性联系起来，可以对复杂的行为进行适当的调整，并可能作为大脑如何在竞争性动机和行动之间确定优先次序的模型。

DESCRIPTION (provided by applicant): 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.