Gustatory Afferent Organization in the Solitary Nucleus

孤核中的味觉传入组织

• 批准号: 7789904
• 负责人: Susan P Travers
• 金额: $ 32.41万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7789904
• 关键词: Affect; Agonist; Area; Behavior; Behavioral; Brain; Brain Stem; Brain region; CTOP; Cells; Characteristics; Complex; Data; Eating; Endorphins; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalins; Facial nerve structure; Feeding behaviors; Fiber; Food; Frequencies; Globus Pallidus; Goals; Health; Human; Immunohistochemistry; In Vitro; Infusion procedures; Injection of therapeutic agent; Investigation; Knowledge; Label; Length; Ligands; Measures; Mechanical Stimulation; Membrane; Motor; Movement; Neuraxis; Neuromodulator; Neuromodulator Receptors; Neurons; Neuropeptide Receptor; Neurotransmitters; Nucleus Accumbens; Nucleus solitarius; Opiates; Opioid; Opioid Peptide; Opioid Receptor; Oral; Outcome; Pathway interactions; Pattern; Phase; Pontine structure; Population; Preparation; Process; Property; Prosencephalon; Rattus; Reticular Formation; Sensory; Signal Transduction; Site; Slice; Stimulus; Structure; Taste Perception; Testing; To specify; Tracer; Transgenic Mice; Work; base; behavior measurement; cell type; computerized data processing; cysteinyltyrosine; feeding; gamma-Aminobutyric Acid; hindbrain; hypoglossal nucleus; in vivo; neurophysiology; neuroregulation; nutrition; oral sensory; parabrachial nucleus; patch clamp; preference; public health relevance; receptive field; receptor; relating to nervous system; research study; response; somatosensory; synthetic enzyme

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: The rostral portion of the nucleus of the solitary tract is the initial termination site of all primary afferent fibers conveying gustatory information. Good nutrition is critical to health, and the sense of taste profoundly impacts the type and amount of food eaten. This project will focus on how one class of opiate peptides known to promote eating, influences this region of the brain.

描述（由申请方提供）：阿片肽与阿片受体（MORs）相互作用，影响食物摄入。对这些影响的基础的一种解释是，它们影响食物的适口性。前脑结构，特别是脑桥核和腹侧苍白球，包括一个关键的基板上的MORs的进食效果。然而，内啡肽也通过脑干回路影响进食，尽管这些影响的位点，效果和机制尚不清楚。一个候选脑干区域包括孤束吻侧核（rNST）中的味觉神经元和下丘脑网状结构（RF）中的嗅觉回路，这是一个功能整合的区域，我们称之为“吻侧孤束复合体”（RSC）。先前的研究表明，将莫尔激动剂注射到该附近增加食物摄入，而拮抗剂具有相反的效果。然而，更精确的注射和行为测量的初步数据表明，向RSC中输注莫尔激动剂产生多种影响，包括更能指示摄食抑制的即时效应。我们假设，这些复杂的影响反映了这些配体在多个点在这个异质电路的相互作用。本建议的目标是精确地定义在rNST和subjunctiveRF中操纵MORs的行为后果，并指定这些效应的位点和细胞基础。具体目标是：（1）通过进行莫尔激动剂（DAMGO）和拮抗剂（CTOP）的小（60 nl）输注，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，分析操纵rNST和皮下RF中的MOR的感觉和运动后果。(2)建立DAMGO和CTOP局部注射对体内制备的rNST和RF中的单单位味觉和口腔体感反应的影响，以及（3）从rNST和皮下RF进行体外膜片钳记录，以表征通过其传入和传出连接识别的神经元的莫尔调节的细胞基础。以前的工作，包括在最后一个项目期间完成的研究，已经澄清了脑干味觉神经元的神经生理反应特性和连接，但中枢味觉回路中神经递质功能的知识是稀缺的。拟议中的实验将开始填补这一空白。此外，这些研究将有助于理解进食的神经控制，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的，涉及中枢神经系统多个区域和水平之间的相互作用。味觉对这种行为有重要影响，rNST是处理这些感觉信号的第一个中心部位。潜在的RF包含运动电路，其包括整合前脑和后脑信号的最终共同通路，该信号决定食物摄入是继续还是中止。这个提议的目标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相互作用。 公共卫生相关性：孤束核的吻侧部是所有传递味觉信息的初级传入纤维的起始终止部位。良好的营养对健康至关重要，味觉对所吃食物的类型和数量有着深刻的影响。该项目将重点关注一类已知促进进食的阿片肽如何影响大脑的这一区域。