Physiology of Raphe Magnus Cells During Wake and Sleep

描述（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，如何选择和完成一个行动模式。这项建议测试新的假设，即延髓中缝大肌（RM）捍卫食物消费分心，因此有助于肥胖，但这一功能不从事疾病或恶心时厌食症的发生。进食和对中等伤害性刺激的反应在对生存和紧迫性的重要性方面很好地匹配，并且都是实验上易于处理的。我们以前表明，从有害的热撤退在大鼠喂养过程中受到抑制，RM细胞是这种抑制所必需的。本项目旨在进一步研究这种现象，在健康和生病的大鼠喂养自由。为了测试大鼠是否需要自我启动进食以触发RM疼痛抑制，Aim 1将比较安静清醒期间对有害热的反应和口服输注物质的摄入。这一目标还将测试饥饿、营养成分、适口性和口舌运动如何影响食物消耗过程中疼痛反应的抑制。将在清醒的行为大鼠中记录RM细胞，以确定在口服输注物的消耗期间疼痛抑制性OFF细胞是否被兴奋并且疼痛促进性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降低食物的显著性如何改变进食期间疼痛反应的抑制以及RM细胞活性。初步结果表明，RM介导的戒断抑制在摄入蔗糖，水或糖精，独立的饥饿或营养价值，但撤回过程中不抑制奎宁输液。目标2将确定RM的进食防御是否被恶心、疾病或与疾病相关的线索关闭。初步数据表明，戒断抑制不伴随摄入时，动物是生病或呕吐或在存在疾病相关的线索，这表明RM细胞放电的变化，通常伴随食物消费不发生在这些健康条件下。将感官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，可以进行适当的调整，以参与复杂的行为，并可以作为大脑如何确定竞争动机和行动之间的优先级的模型。

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.