SWALLOWING & ESOPHAGEAL PERISTALSIS--BRAINSTEM CIRCUITRY

吞咽，一种更复杂的运动行为，是被编程的 中心由位于其内部和周围的髓中心图案生成器 孤束核孤束核信号的产生和调制 中枢模式生成器的神经元模式运动活动是 依赖于内源性的兴奋和抑制机制 必需的中枢和外周传入触点。一个重要的 NMDA和NMDA对激发的相对贡献不平衡 通过GABA受体的抑制可能形成功能障碍的基础 吞咽出现在神经系统疾病中。把老鼠当作动物来利用 兴奋和抑制过程的解剖学基础模型 口咽期和食道期的协调至关重要 吞咽的可能性将会被研究。伪狂犬病的跨突触追踪 病毒结合：(1)荧光逆行追踪 用来研究颊咽之间的解剖联系 和位于运动前神经元的食道中枢模式发生器网络 水平；(2)寡核苷酸探针原位杂交 不同的N-甲基-D-天冬氨酸(NMDA)受体亚基(R1、R2A-D)和 GABAA受体亚单位(α1-6、β1-3、γ1-3、增量)将是 用来确定NMDA和GABAA受体亚基的表达 (3)谷氨酸和GABA的免疫细胞化学 用来确定谷氨酰胺能和组织 GABA能神经元构成并投射到中枢模式 (4)NMDAR1受体蛋白和 烟酰胺腺嘌呤二核苷酸磷酸黄递酶(NADPH-d) 一氧化氮合酶的组织化学(三标记法) 用于确定NMDAR1之间的解剖关系 运动前神经元的受体蛋白和一氧化氮合酶。硝酸盐 响应NMDA受体激活的氧化物产生起着重要作用 突触化学信号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变化 功能可能与吞咽障碍的发病机制有关， 这些研究可能对未来的临床治疗有直接的影响。 吞咽困难的患者。

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.