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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK044487-02
Application #
3246008
Study Section
Sensory Disorders and Language Study Section (CMS)
Project Start
1992-02-01
Project End
1996-01-31
Budget Start
1993-02-01
Budget End
1994-01-31
Support Year
2
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Children's Hospital of Philadelphia
Department
Type
DUNS #
073757627
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Weyler, R T; Yurko-Mauro, K A; Rubenstein, R et al. (1999) CFTR is functionally active in GnRH-expressing GT1-7 hypothalamic neurons. Am J Physiol 277:C563-71
Broussard, D L; Lynn, R B; Wiedner, E B et al. (1998) Solitarial premotor neuron projections to the rat esophagus and pharynx: implications for control of swallowing. Gastroenterology 114:1268-75
Broussard, D L; Bao, X; Altschuler, S M (1998) Somatostatin immunoreactivity in esophageal premotor neurons of the rat. Neurosci Lett 250:201-4
Broussard, D L; Li, H; Altschuler, S M (1997) Colocalization of GABA(A) and NMDA receptors within the dorsal motor nucleus of the vagus nerve (DMV) of the rat. Brain Res 763:123-6
Broussard, D L; Li, X; Altschuler, S M (1996) Localization of GABAA alpha 1 mRNA subunit in the brainstem nuclei controlling esophageal peristalsis. Brain Res Mol Brain Res 40:143-7
Mulberg, A E; Resta, L P; Wiedner, E B et al. (1995) Expression and localization of the cystic fibrosis transmembrane conductance regulator mRNA and its protein in rat brain. J Clin Invest 96:646-52
Fine, D M; Lo, C F; Aguillar, L et al. (1995) Cellular chloride depletion inhibits cAMP-activated electrogenic chloride fluxes in HT29-18-C1 cells. J Membr Biol 145:129-41
Wiedner, E B; Bao, X; Altschuler, S M (1995) Localization of nitric oxide synthase in the brain stem neural circuit controlling esophageal peristalsis in rats. Gastroenterology 108:367-75
Bao, X; Wiedner, E B; Altschuler, S M (1995) Transsynaptic localization of pharyngeal premotor neurons in rat. Brain Res 696:246-9
Gesser, R M; Valyi-Nagy, T; Fraser, N W et al. (1995) Oral inoculation of SCID mice with an attenuated herpes simplex virus-1 strain causes persistent enteric nervous system infection and gastric ulcers without direct mucosal infection. Lab Invest 73:880-9

Showing the most recent 10 out of 16 publications