GASTRIC FUNCTION--CENTRAL CONTROL

胃功能——中枢控制

• 批准号: 3409221
• 负责人: Richard C. Rogers
• 金额: $ 15.89万
• 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: 1986-07-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3409221
• 关键词: bombesin; calcitonin; cerebellar cortex; constipation; diarrhea; dorsal raphe nucleus; duodenal ulcer; electrophysiology; enkephalins; environmental stressor; gastric acid; gastrins; gastrointestinal function; gastrointestinal pharmacology; hormone inhibitor; hypothalamus; immunocytochemistry; laboratory rat; limbic system; microelectrodes; microinjections; neural information processing; neuropeptides; neurophysiology; neurotensin; neurotransmitter receptor; paraventricular nucleus; peptic ulcer; prosencephalon; secretion; sensorimotor system; sleep regulatory center; somatostatin; stomach motility /pressure; vagus nerve

Gastrointestinal secretory and motor functions are markedly altered in response to various environmental stressors and to changcs in behavioral arousal. It follows that the brain regions responsible for interpreting the significance of events external to the organism might also modiate thc changes in gastrointestinal function. Several forebrain nuclei are thought to be involved in the adjustment of thc "internal milieu" to support changes in behavior demanded by the environment. Three of these structures will be addressed in this proposal: the paraventricular nuctcus of the hypothalamus (PVN), the central nucieus of the amygdala (CNA), and the bed nucleus of the stria terminalis (BST). Available anatomical and physiological evidence indicates that all of these brain regions send direct, monosynaptic input to the brainstem vagal nuclei, which are critical in the parasympathetic control of the gastrointestinal tract. In addition, the nucleus raphe obscurus (nRO), which may bc part of a ncural circuit controlling the production and maintenancc of the sleep-walking cycle, also maintains a direct connection with the vagal nuclei. Immunocytochemical studies have identified those four structures as sources of peptidergic innervation of the vagal sensorimotor nuclei. Recent physiological studies imply that many of the peptides contained within these sources of input to vagal neurons significantly alter gastrointestinal function. Our goal is to establish specifically how these peptide-containing pathways influence the activity of identifiable components of the vagal circuits which control gastrointestinal function. We will pursue this goal by using electrophysiological and gastroenterological methods in combination with a technique for quantitative micropressure injection of peptides (and their antagonists) into physiologically-identified clusters of vagal sensory and motor neurons. By applying these methods, we may begin to elucidate the details of central peptidergic modulation of brainstem circuits which control the gastrointestinal tract. Such information will be essential to ultimately understand how the brain is implicated in dysfunctional states such as diarrhea, constipation and ulcer.

胃肠道分泌和运动功能显着改变 对各种环境压力源和行为变化的反应 唤醒。由此可见，负责解释的大脑区域 有机体外部事件的重要性也可能会调节 胃肠道功能发生变化。前脑有几个核团 被认为参与了“内部环境”的调整 支持环境所要求的行为改变。其中三个 本提案将讨论的结构：室旁 下丘脑核 (PVN)，杏仁核的中央核 (CNA) 和终纹床核 (BST)。可用的 解剖学和生理学证据表明，所有这些大脑 区域向脑干迷走神经核发送直接的单突触输入， 这对于副交感神经对胃肠道的控制至关重要 道。此外，中缝暗核（nRO），可能是 控制生产和维护的神经电路 梦游周期，也与迷走神经保持直接联系 原子核。 免疫细胞化学研究已确定这四种结构： 迷走神经感觉运动核的肽能神经支配的来源。 最近的生理学研究表明，许多肽含有 在这些迷走神经元的输入来源中显着改变 胃肠功能。 我们的目标是明确这些含有肽的物质如何 通路影响迷走神经可识别成分的活动 控制胃肠功能的电路。我们将追求这个 通过使用电生理学和胃肠病学方法来实现目标 与定量微压注射技术相结合 将肽（及其拮抗剂）分解成生理学鉴定的簇 迷走神经感觉和运动神经元。通过应用这些方法，我们可以 开始阐明中枢肽能调节的细节 控制胃肠道的脑干回路。这样的 信息对于最终了解大脑的运作方式至关重要 与腹泻、便秘等功能失调状态有关 溃疡。