The long rang goal of this applicant is to elucidate the mechanisms responsible for the generation and control of respiration. The specific goal of this project is to DETERMINE THE CENTRAL NERVOUS SYSTEM STRUCTURES INVOLVED IN THE TRANSIENT INHIBITION AND/OR TERMINATION OF INSPIRATORY MOTOR DISCHARGE ELICITED BY VARIOUS AFFERENTS. These afferents are important in the normal regulation of respiratory pattern. In addition they have been implicated in pathologic conditions such as sleep apneas and sudden infant death syndrome. An early termination of inspiratory motor drive can be elicited by stimulation of afferent fibers in the vagus nerve, the superior laryngeal nerve (SLN), and the intercostal nerves (ICN). Stimulation of these nerves has been utilized extensively in the study of the mechanisms involved in termination of inspiratory discharge. The SLN and ICN afferents as well as the phrenic nerve afferents also elicit a transient reduction of inspiratory discharge in response to a single shock. Since all four afferent systems have been demonstrated to affect respiratory neuronal discharge in the nucleus tractus solitarius (NTS), a prevalent assumption has been that the reflex effects are mediated through this nucleus. However, recent studies demonstrate that the phase-switching effects of SLN and vagal afferents are not compromised by extensive lesions of the vlNTS. This observation prompts the hypothesis that the reflex effects evoked by many peripheral afferents are likely to be mediated by brainstem nuclei other than the vlNTS. These experiments are designed to specifically investigate the AFFERENT INHIBITION of inspiration, which is likely to involve different mechanisms than those used for normal inspiratory termination in the reduced, anesthetized, unperturbed cat. For each of the four afferent systems, this project will examine the potential role of the pontine respiratory group, the medial NTS and the Botzinger Complex since indirect evidence suggests the involvement of each of these regions. Radio frequency lesions, electrolytic microlesions and chemical lesions will be utilized to examine the involvement of likely nuclei in the afferent inhibitory effects. These lesioning techniques will be supplemented with nerve and extracellular neuronal recordings.
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NIH ExPorter