Gustatory Afferent Organization in the Solitary Nucleus

阿片肽与阿片受体（MORs）相互作用，影响食物摄取。一个解释的基础 这些影响之一是它们影响食物的适口性。前脑结构，尤其是脑桥核 和腹侧苍白球，构成了MORs对摄食影响的关键底物。然而，尽管如此， 内啡肽也通过脑干回路影响进食，尽管这些神经递质的位点、作用和机制还不清楚。 影响不太明显。一个候选的脑干区域包括位于小脑顶核的吻侧核中的味觉神经元。 孤束（rNST）和延髓下网状结构（RF）（一个功能整合区域）中的orbian回路 我们称之为“喙孤波”先前的研究表明，向该组织中注射莫尔激动剂， 邻近增加食物摄入，而拮抗剂具有相反的效果。更精确的初步数据 然而，注射和行为测量反而表明，向RSC中输注莫尔激动剂可发挥 多重影响，包括更能表明摄食抑制的即时影响。我们假设 这些复杂的效应反映了这些配体在这种异质结构中的多个点上的相互作用， 电路本提案的目标是精确定义以下行为的行为后果： 操纵rNST和subjunctiveRF中的MORs，并指定这些MORs的位点和细胞基础， 方面的影响.具体目的是：（1）分析操纵MORs的感觉和运动后果 通过少量（60 nl）输注莫尔激动剂（DAMGO）和拮抗剂， （CTOP），并使用多种行为措施，包括味觉反应和短期味觉偏好 试验. (2)确定局部注射DAMGO和CTOP对单单位味觉和口腔的影响 在体内制备的rNST和RF中的体感反应，和（3）进行体外膜片钳 来自rNST和脑下RF的记录以表征神经元的莫尔调节的细胞基础 通过它们的传入和传出连接来识别。以往的工作，包括过去一年完成的研究 项目期间，阐明了脑干味觉的神经生理反应特性和连接性 但是关于中枢味觉回路中神经递质功能的知识很少。拟议 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系统的 控制进食，这是一种深刻影响人类健康的行为。调节进食的神经基质是 复杂，涉及中枢神经系统的多个区域和水平之间的相互作用。品味有一个 rNST是这些感觉信号的第一个中心部位， 已处理。基础RF包含运动电路，其包括整合 前脑和后脑发出信号，决定食物摄入是继续还是中止。这个目标 我们的建议是了解一类在进食中很重要的神经调质，阿片配体，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.