AUTONOMIC REGULATION OF FOOD INTAKE AND METABOLISM

最近从过于中间派到更全面的方法的转变 能量和营养动态平衡强调了迷走神经和 参与肠道/大脑交流的其他内脏传入神经。迷路的 感觉纤维在传递饱腹感信号方面尤为重要。 从处理食物的内脏到大脑，因此起到了 在控制膳食数量和可能的总体能量方面发挥重要作用 入口处。拟议研究的总体目标是确定 从外周到行为的完整信号通路 行动。这包括a)解剖和神经化学鉴定 所有参与的神经元组；b)编码和解码分析 感官信息的原理；以及c)演示如何 信号被转化为摄取和其他行为行为。 虽然过去的工作主要集中在外周的解剖学方面 迷走神经传入纤维的神经支配模式 格兰特专注于胃肠迷走神经感觉的处理 尾侧脑干中的信息。它将检验这一假设 不同的营养素和其他外周刺激使用解剖学和/或 从神经化学上分离出通往大脑的信号通路。二次订购 尾侧脑干中接收特定感觉信号的神经元 来自胃肠道的补体将被识别 解剖和功能方法，如跨突触病毒追踪 C-fos诱导。识别出的神经元将被描述为 对其神经化学表型的敏感性原位检测 神经递质的杂交和免疫细胞化学方案， 多肽及其受体。他们的轴突投射将被映射 使用逆行追踪法。最后，政府的参与 与感觉迷走神经相关的特定递质和受体 控制摄食行为的途径将直接进行测试。 尤其是谷氨酸及其受体亚型在体内的作用。 将通过以下方式分析各种喂养模式的饱和过程 在计算机监测中测量进食的微观结构 固体和液体食品的系统。其中的研究建议 应用将填补我们在神经控制知识方面的重要空白 食物摄入量和体重以及消化、吸收和 胃肠道的防御机制。因此，它有 有潜力在这场斗争中刺激新治疗手段的发展 对抗人类疾病，如肥胖及其继发性并发症， 神经性厌食症、摄入和心脏灼热以及炎症性肠炎 疾病。

The recent shift from an overly centrist to a more holistic approach to energy and nutrient homeostasis has emphasized the role of vagal and other visceral afferents involved in gut/brain communication. Vagal sensory fibers are particularly important in relaying satiety signals from the food handling viscera to the brain and therefore play an important role in the control of meal size and possibly overall energy intake. The overall objective of the proposed research is to identify the complete signaling pathway from the periphery to the behavioral action. This includes a) anatomical and neurochemical identification of all participating neuron groups; b) analysis of coding and decoding principles of sensory information; and c) demonstrating how these signals are translated into ingestive and other behavioral actions. While past work mainly focused on anatomical aspects of the peripheral innervation pattern of vagal afferent fibers, the work proposed for this grant focuses on processing of gastrointestinal vagal sensory information in the caudal brainstem. It will test the hypothesis that different nutrients and other peripheral stimuli use anatomically and/or neurochemically separate signaling pathways to the brain. Second order neurons in the caudal brainstem that receive specific sensory signals from the gastrointestinal tract will be identified by complementary anatomical and functional approaches such as transynaptic viral tracing and c-fos induction. Identified neurons will then be characterized as to their neurochemical phenotype by using sensitive in situ hybridization and immunocytochemistry protocols for neurotransmitters, peptides and their receptors. Their axonal projections will be mapped with the use of retrograde tracing. Finally, the involvement of specific transmitters and receptors associated with the sensory vagal pathways in the control of ingestive behavior will be directly tested. In particular, the role of glutamate and its receptor subtypes in the process of satiation of various feeding paradigms will be analyzed by measuring the microstructure of meal taking in computerized monitoring systems for both solid and liquid foods. The research proposal in this application will fill important gaps in our knowledge of neural control of food intake and body weight as well as digestive, absorptive and defense mechanisms of the gastrointestinal tract. It has therefore, the potential to spur the development of new therapeutic means in the fight against human diseases such as obesity and its secondary complications, anorexia nervosa, ingestion and heart burn, and inflammatory bowel disease.