BRAINSTEM NEURAL NETWORKS AND AIRWAY DEFENSIVE REFLEXES

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The goal of this research is to define the functional organization and internal operations of the brainstem network through which airway defensive reflex motor patterns are generated and modulated. Many-neuron recording technology and spike train analysis methods (i.e., cross-correlation, gravity) will be used to determine parallel and sequential neuronal responses during fictive cough and the laryngeal expiration reflex, and the define concurrent functional interactions among physiologically characterized neurons in several brainstem regions. The plausibility of network models derived from this approach will be tested with computer simulations. Fictive cough and the expiration reflex will be evoked by mechanical stimulation of the intrathoracic trachea and larynx, respectively, in decerebrated, paralyzed, ventilated cats. Hypothesis I. Botzinger/ventral respiratory group (BOT/VRG) network interactions produce the cough patterns that are relayed to spinal respiratory motoneurons. Hypothesis II. Laryngeal motoneuron activity during cough is controlled by BOT/VRG propriobulbar neurons. Hypothesis III. Cough receptors activate neurons in the caudal nucleus tractus solitarius (NTS) which distribute information concurrently to neurons in the dorsal respiratory group (DRG), and pontine respiratory group (PRG). Hypothesis IV. Functional connectivity among PRG neurons contribute to their respiratory modulation, and are similar to interactions among rhythm/pattern generating BOT/VRG neurons. Hypothesis V. The PRG modulates the BOT/VRG generated cough motor pattern through divergent actions of specific neurons uon the and raphe nuclei. Hypothesis VI. The raphe neuronal network is modulated during cough by inputs from NTS, PRG, and BOT/VRG. Hypothesis VII. The raphe neuronal network modulates the cough motor pattern through actions on the BOT/VRG. Other Parallel Studies: In the course of the planned experiments, we will also examine brainstem mechanisms that generate laryngeal expiration reflex motor patterns. Airway defensive reflexes are essential for the day-to-day survival of individuals with and without lung disease; they can also exacerbate other pathological conditions. These studies will contribute basic information that could be useful for future development of more effective therapeutic interventions for disorders involving these reflexes.