Gustatory Afferent Organization in the Solitary Nucleus

阿片肽与M阿片受体(MORS)相互作用，影响食物的摄取。对这一基础的一种解释 这些影响之一是它们影响了食物的适口性。前脑结构，尤其是伏隔核 腹侧苍白球是MORS影响摄食的关键底物。不过， 内啡肽也通过脑干回路影响进食，尽管它们的位置、作用和机制 影响就不那么明显了。一个候选的脑干区域包括位于丘脑吻侧核的味觉神经元。 下层网状结构(RF)中的孤束(RNST)和运动回路(RF)是一个功能整合的区域 这就是我们所说的“鸟嘴孤独复合体”(RSC)。先前的研究表明，向脑内注射MOR激动剂 邻近地区会增加食物的摄入量，而拮抗剂的作用则相反。初步数据更准确 然而，注射和行为测量表明，向RSC注入MOR激动剂会产生 多重影响，包括直接影响，更多地表明对进食的抑制。我们假设 这些复杂的效应反映了这些配体在多个点上的相互作用 电路。本提案的目标是准确定义以下行为后果 操纵RNST和下层RF中的MORS，并指定它们的位置和细胞基础 效果。具体目的是：(1)分析操纵MORS的感觉和运动后果 通过小剂量(60nl)输注MOR激动剂(DAMGO)和拮抗剂 (CTOP)，并使用多种行为测量，包括味觉反应性和短期味觉偏好 测试。(2)建立局部注射DAMGO和CTOP对单位味觉和口腔的影响 体内制剂中RNST和RF的体感反应，以及(3)体外膜片钳 来自RNST和下层RF的记录以表征神经元MOR调制的细胞基础 通过它们的传入和传出连接来识别。以前的工作，包括在过去一年中完成的研究 项目期内，已经阐明了脑干味觉的神经生理反应特性和连通性 但关于中枢味觉回路中神经递质功能的知识却很少。建议数 实验将开始填补这一空白。此外，这些研究将有助于理解神经 控制喂食，这是一种深刻影响人类健康的行为。调节饮食的神经底物是 复杂，涉及多个区域和水平的中枢神经系统之间的相互作用。品味有一种 对这种行为的主要影响，RNST是这些感觉信号的第一个中枢部位 已处理。底层RF包含马达电路，该马达电路包括最终公共路径 前脑和后脑发出的信号决定食物的摄入是继续还是中止。这样做的目的是 建议是了解一类在摄食中重要的神经调节剂，即阿片类配体，如何在 这些关键节点。

Opiate peptides, interacting with m opiate receptors (MORs), affect food intake. One explanation for the basis of these effects is that they influence food palatability. Forebrain structures, especially nucleus accumbens and the ventral pallidum, comprise a critical substrate for the effect of MORs on feeding. Nevertheless, endorphins also impact eating through brainstem circuits, although the loci, effects, and mechanisms of these influences are less clear. One candidate brainstem region includes taste neurons in the rostral nucleus of the solitary tract (rNST) and oromotor circuitry in subjacent reticular formation (RF), a functionally-integrated region that we call the "rostral solitary complex" (RSC). Previous studies suggest that injecting MOR agonists into this vicinity increases food intake whereas antagonists have the opposite effect. Preliminary data with more precise injections and behavioral measures, however, instead suggest that MOR agonist infusions into the RSC exert multiple influences, including immediate effects more indicative of a suppression of feeding. We hypothesize that these complex effects reflect the interaction of these ligands at multiple points in this heterogeneous circuitry. The goal of the present proposal is to precisely define the behavioral consequences of manipulating MORs in the rNST and subjacent RF and to specify the sites and cellular basis of these effects. The Specific Aims are to: (1) Analyze the sensory and motor consequences of manipulating MORs in the rNST and subjacent RF by making small (60nl) infusions of MOR agonists (DAMGO) and antagonists (CTOP), and using multiple behavioral measures, including taste reactivity and short-term taste preference tests. (2) Establish the impact of local injections of DAMGO and CTOP on single-unit gustatory and oral somatosensory responses in the rNST and RF in an in vivo preparation, and (3) Perform in vitro, patch-clamp recordings from the rNST and subjacent RF to characterize the cellular basis of MOR modulation of neurons identified by their afferent and efferent connectivity. Previous work, including studies completed during the last project period, has clarified neurophysiological response properties and connectivity of brainstem taste neurons but knowledge about neurotransmitter function in central taste circuits is scarce. The proposed experiments will begin to fill this void. Moreover, these studies will contribute to understanding of the neural control of feeding, a behavior profoundly impacting human health. The neural substrate regulating eating is complex, involving interactions between multiple regions and levels of the central nervous system. Taste has a major influence on this behavior and the rNST is the 1st central site where these sensory signals are processed. The underlying RF contains motor circuitry comprising a final common pathway that integrates forebrain and hindbrain signals determining whether food intake continues or is aborted. The goal of this proposal is to understand how one class of neuromodulators important in feeding, m opiate ligands, interact at these critical nodes.