Physiology of Raphe Magnus Cells During Wake and Sleep

描述(由申请人提供)：生物学中的一个核心问题是解释在存在相互冲突的目标的情况下如何选择和完成动作模式。这项提议检验了新的假设，即延髓中缝大核(RM)保护食物消耗不受分心，从而导致肥胖，但这一功能在疾病或厌食症发生时恶心时不参与。在对生存的重要性和紧迫感方面，摄食和对中等有害刺激的反应很好地匹配，而且在实验上都是容易驯服的。我们之前的研究表明，大鼠在进食过程中，从毒热中撤退会受到抑制，这种抑制需要RM细胞。该项目旨在进一步研究随意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主动进食以触发RM疼痛抑制，目标1将比较安静清醒和摄入口腔内输液物质时对有毒热量的反应。这一目标还将测试饥饿、营养成分、适口性和口腔运动如何影响食物消费过程中疼痛反应的抑制。清醒状态的大鼠将记录RM细胞，以确定在口服输液过程中，疼痛抑制细胞是否兴奋，而疼痛促进细胞是否受到抑制。这次修订中增加的实验将测试增加疼痛刺激的强度和持续时间或降低食物的显着性如何改变对疼痛反应的抑制以及喂养期间RM细胞的活动。初步结果表明，在摄入蔗糖、水或糖精的过程中，RM介导了戒断抑制，而不受饥饿或营养价值的影响，但在奎宁的输注过程中，戒断并不被抑制。目标2将确定RM对进食的防御是否因恶心、疾病或与疾病相关的提示而关闭。初步数据表明，当动物生病或恶心或存在与疾病相关的线索时，戒断抑制不会伴随着摄入，这表明在这些健康状况下，通常伴随食物消费的RM细胞放电的变化不会发生。将感觉调节与不同健康条件(幸福、疾病)下进食的竞争性突显联系起来，可以适当地调整以处理复杂的行为，并可以作为大脑如何在相互竞争的动机和行动之间确定优先顺序的模型。

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.