AIRWAYS CENTRAL NERVOUS SYSTEM CONTROL

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This investigation consists of two major lines of research focused on the same problem: the analysis of CNS control of the airways. The first part of this grant application deals with neuroanatomy of central airway pathways and the second part is focused on determining the functional role some of the specific CNS regions play in regulation of secretomotor and bronchomotor control. Anatomical studies will use pseudorabies virus as a transneuronal marker to study the cells of origin which control the parasympathetic outflow to the intrathoracic airways (bronchus and distal most part of the airways) as well as the trachea. Potential differences in innervation of the tracheobronchial system will be analyzed. A detailed study of the neuropeptide-containing premotor neurons innervating the tracheal parasympathetic preganglionic neurons will be made using immunohistochemical procedures to identify both virally infected neurons and putative neurotransmitters. Finally, the chemical content of the tracheal parasympathetic preganglionic neurons will be examined using choline acetyltransferase and neuropeptide immunochemistry combined with cholera-toxin retrograde cell body labeling. In the second part, secretomotor and bronchomotor functions will be investigated following L-glutamate stimulation of specific brain nuclei known to project to airway parasympathetic preganglionic neurons. Furthermore, their role in reflex responses will be studied. The first project will involve an analysis of the midline nuclei, with particular attention focused on the raphe pallidus and adjoining region. The second project involves an analysis of the Kolliker-Fuse nucleus and surrounding region. The third project will analyze the responses elicited from the dorsal periventricular gray matter. A fourth project will analyze the role of excitatory amino acids in generation of parasympathetic activity and in mediating secretomotor and bronchomotor reflex responses. The data derived from these studies will provide a better understanding of the CNS neural systems that influence airway function and have a direct bearing on understanding centrally mediated airways dysfunctions.