SWALLOWING & ESOPHAGEAL PERISTALSIS--BRAINSTEM CIRCUITRY

吞咽

• 批准号: 2518312
• 负责人: STEVEN M ALTSCHULER
• 金额: $ 18.74万
• 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 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2518312
• 关键词: GABA receptor; NAD(H) phosphate; NMDA receptors; afferent nerve; brain regulatory center; fluorescent dye /probe; gamma aminobutyrate; gastrointestinal motility /pressure; glutamates; histochemistry /cytochemistry; immunocytochemistry; in situ hybridization; innervation; interneurons; laboratory rat; motor neurons; neural information processing; neuroanatomy; nitric oxide synthase; receptor expression; sensorimotor system; sensory mechanism; suid alphaherpesvirus 1; swallowing; synapses

Swallowing, one of the more complex motor behaviors, is programmed centrally by a medullary central pattern generator located in and around the nucleus of the solitary tract. The generation and modulation of neuronal patterned motor activity by the central pattern generator is dependent upon endogenous excitatory and inhibitory mechanisms and requisite central and peripheral afferent contacts. A significant imbalance in the relative contribution of excitation via NMDA and inhibition via GABA receptors may form the basis of dysfunctional swallowing present in neurological disease. Utilizing the rat as animal model, the anatomic basis of the excitatory and inhibitory processes critical to the coordination of the buccopharyngeal and esophageal phases of swallowing will be studied. Transsynaptic tracing with Pseudorabies Virus in conjunction with: (1) Fluorescent retrograde tracing will be utilized to study the anatomical connections between the buccopharyngeal and esophageal central pattern generator networks at the premotor neuron level; (2) In situ hybridization with oligonucleotide probes for the different N-Methyl-D-aspartate (NMDA) receptor subunits (R1, R2A-D) and GABAA receptor subunits (alpha1-6, Beta1-3, gamma1-3, delta) will be utilized to determine the NMDA and GABAA receptor subunits expressed by premotor neurons;(3) immunocytochemistry for glutamate and GABA will be utilized to determine location and organization of glutaminergic and GABAergic neurons constituting and projecting to the central pattern generator; (4) immunocytochemistry for NMDAR1 receptor protein and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry (triple labeling method) for nitric oxide synthase will be utilized to determine the anatomic relationship between the NMDAR1 receptor protein and nitric oxide synthase in premotor neurons. Nitric oxide production in response to NMDA receptor activation plays a prominent role in chemical synaptic signaling and integration of neuronal activity. Since alterations in excitatory and inhibitory synaptic function could contribute to the pathogenesis of swallowing disorders, these studies may have a direct bearing on the future clinical management of patients with dysphagia.

吞咽是一种更复杂的运动行为， 通过位于髓内和周围的髓中央模式发生器 孤束核的产生和调制 由中央模式发生器进行的神经元模式化运动活动是 依赖于内源性兴奋和抑制机制， 必要的中枢和外周传入联系。显著 通过NMDA的兴奋的相对贡献的不平衡， 通过GABA受体的抑制可能形成功能障碍的基础， 吞咽存在于神经系统疾病中。利用大鼠作为动物 模型，兴奋和抑制过程的解剖学基础 对于协调颊咽期和食管期至关重要 将被研究。伪狂犬病的跨突触追踪 病毒结合：（1）荧光逆行追踪将 用于研究颊咽之间的解剖连接 和食管中枢模式发生器网络在前运动神经元 （2）用寡核苷酸探针进行原位杂交， 不同的N-甲基-D-天冬氨酸（NMDA）受体亚基（R1，R2 A-D）， GABAA受体亚单位（α 1 -6、β 1 -3、γ 1 -3、δ）将被 用于确定表达的NMDA和GABAA受体亚单位， 运动前神经元;（3）免疫细胞化学的谷氨酸和GABA将是 用于确定多巴胺能神经元的位置和组织， GABA能神经元构成并投射到中枢模式 （4）NMDAR 1受体蛋白的免疫细胞化学， 烟酰胺腺嘌呤二核苷酸磷酸黄递酶 一氧化氮合酶组织化学（三重标记法）将 用于确定NMDAR 1之间的解剖关系 受体蛋白和一氧化氮合酶。硝酸 响应于NMDA受体激活的氧化物产生起作用， 在化学突触信号传导和神经元整合中的重要作用 活动由于兴奋性和抑制性突触的改变， 功能可能有助于吞咽障碍的发病机制， 这些研究可能对未来的临床管理有直接影响 有吞咽困难的病人。