SWALLOWING & ESOPHAGEAL PERISTALIS--BRAINSTEM CIRCUITRY

吞咽

• 批准号: 2143829
• 负责人: STEVEN M ALTSCHULER
• 金额: $ 17.1万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-02-01 至 1996-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2143829
• 关键词: acetylcholine; afferent nerve; brain regulatory center; calcitonin gene related peptide; central neural pathway /tract; colchicine; enkephalins; fluorescent dye /probe; gastrointestinal motility /pressure; histochemistry /cytochemistry; horseradish peroxidase; immunocytochemistry; immunofluorescence technique; innervation; interneurons; laboratory rat; motor neurons; neural information processing; neuroanatomy; neuropeptides; somatostatin; substance P; suid alphaherpesvirus 1; swallowing; synapses; tissue /cell preparation

Swallowing is a complex motor behavior, characterized by the coordinated contraction of musculature in the mouth, pharynx, larynx, and esophagus. It is well established that the neural apparatus responsible for the initiation and control of the buccopharyngeal and esophageal (primary peristalsis) phases of swallowing are located within the medulla. This central pattern generator (CPG) has been thought of as an interneuronal network, that once stimulated by afferent contacts is capable of orchestrating the successive excitation of motoneurons that result in the stereotyped motor events that characterize swallowing. Despite the electrophysiological localization of the CPG, little is known about the neural connectivity and neurochemistry, involved in this functional circuitry. Utilizing histochemical and immunocytochemical techniques, we propose an analysis of the neural circuitry and the neurotransmitters underlying the control of swallowing using the rat as an animal model. To study the neural circuitry. Pseudorabies virus (PRV), a newly described transsynaptic tracer, will be utilized to determine the interneuronal organization of CPG neurons. Cholera toxin-horseradish peroxidase will be used to determine the dendritic architecture of swallowing motoneurons. The presence of extranuclear dendritic projections and/or intranuclear dendritic bundles would provide, anatomical substrates for the initiation and sequencing of motoneuronal activity. To study the neurotransmitters, double labeling, immunohistochemical techniques will employed to determine the neurotransmitter content of PRV immunoreactive neurons (CPG neuron). A combination of fluorescent tracing and immunocytochemical techniques will be utilized to demonstrate neuropeptide content of the sensory neurons in the NG whose central projections make synaptic contact with CPG neurons. These studies will provide an anatomical and neurochemical analysis of the brainstem circuitry underlying swallowing and thus, may have a direct, bearing on the future clinical management of disorders of oropharyngeal and esophageal function, and gastroesophageal reflux.

吞咽是一种复杂的运动行为，其特点是协调 口腔、咽部、喉部和食道的肌肉组织收缩。 众所周知，负责 颊咽和食管的启动和控制（初级 蠕动）吞咽阶段位于髓质内。 这 中枢模式发生器（CPG）被认为是一种中间神经元 网络，一旦受到传入接触的刺激就能够 协调运动神经元的连续兴奋，从而导致 以吞咽为特征的刻板运动事件。 尽管 关于 CPG 的电生理定位，人们知之甚少 神经连接和神经化学，参与这一功能 电路。 利用组织化学和免疫细胞化学技术，我们 提出对神经回路和神经递质的分析 使用大鼠作为动物模型来控制吞咽。 到 研究神经回路。 伪狂犬病病毒（PRV），一种新描述的 跨突触示踪剂，将用于确定间神经元 CPG 神经元的组织。 霍乱毒素——辣根过氧化物酶 用于确定吞咽运动神经元的树突结构。 核外树突状突起和/或核内树突状突起的存在 树突束将为起始提供解剖学基质 和运动神经元活动的测序。 为了研究神经递质， 双标记、免疫组织化学技术将用于确定 PRV 免疫反应神经元（CPG 神经元）的神经递质含量。 一个 荧光示踪和免疫细胞化学技术的结合将 用于证明感觉神经元的神经肽含量 NG 的中央投射与 CPG 神经元进行突触接触。 这些研究将提供解剖学和神经化学分析 吞咽的脑干回路因此可能具有直接的、 对口咽部疾病的未来临床治疗具有重要意义 食管功能和胃食管反流。