NEURAL GENESIS OF RESPIRATORY RHYTHM

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The general objective is to study the neural basis for generation of respiratory patterns in the mammal, with special reference to: a) switching of the respiratory phases (inspiratory-expiratory [I-E] and expiratory-inspiratory [E-I]); b) augmenting (ramp) and decrementing patterns of I neuron activity. The general method of analysis is to ascertain time relations between different respiratory neuron activities, as influenced by perturbations that change respiratory pattern (e.g. vagal and superior laryngeal inputs that advance or retard phase-switching). The role of several respiratory neuron populations in pattern generation will be studied: 1) ventral respiratory group (VRG) neurons, including airway motoneurons (hypoglossal, laryngeal) and their associated premotor neurons; 2) pontine respiratory group (PRG) neurons (region of Kolliker-Fuse nucleus and nucleus parabrachialis medialis). Respiratory neural activity will be studied in relation to: 1) mechanisms of E-I phase-switching; 2) the slow time course of vagal afferent influence on I-E phase-switching; 3) the graded inhibition of airway motoneurons by vagal afferent inputs, and identification of afferent pathways to these neurons and their premotor neurons; 4) the role of rostral pontine respiratory neurons in phase-switching, and their afferent and efferent relations to medullary respiratory neurons. Experimental analysis will involve: 1) simultaneous recording of multiple signals (unit activity from several microelectrodes, mass activity from several respiratory motor nerves) and application of multiple test procedures; 2) phase-response and phase-locking analysis by use of timed delivery of inputs, with special reference to events immediately preceding the phase transitions; 3) intracellular recording to observe both slow and rapid time courses of events during the silent period of a neuron's activity; 4) study of connectivity by recording from multiple signals and application of cross-correlation and cross-spectral analysis (including detection of monosynaptic relations and use of high-frequency oscillation as a marker of connections). The studies are relevant to control of breathing during physiological and pathophysiological conditions, and in particular to the role of airway motoneurons in controlling airway resistance.