SWALLOWING & ESOPHAGEAL PERISTALIS--BRAINSTEM CIRCUITRY

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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.