MECHANISMS AND SITES OF VENTILATORY NEUROGENESIS

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DESCRIPTION: (adapted from the applicant's abstract) Ventilatory activity can be generated at multiple brainstem sites. Gasping is recorded following the isolation of medulla from pons. A region of the lateral tegmental field is hypothesized to contain the central pattern generator for gasping, which contains pacemaker elements. Studies will evaluate further these hypotheses by characterizing the neuronal activities and afferent and efferent projections from this region. Evaluations of gasping may provide insights into the neurogenesis of all patterns of automatic ventilatory activity. Even if pacemaker elements do underlie ventilatory neurogenesis, neuronal circuits define the phasic periods of inspiration and expiration and shape respiratory-modulated neural discharge patterns. In this context, neurons of the rostral pontile "pneumotaxic center" exercise multiple functions in ventilatory control and, possibly, neurogenesis. Such functions include the onset and terminations of inspiration, integration of central chemoreceptor afferent stimuli, and onset of spinal expiratory neural activities. The hypothesis will be evaluated that these multiple functions are regulated by different subpopulations within the pneumotaxic system. The question of subpopulations will also be examined in studies concerning the neural circuit which is responsible for the definition of expiratory activities. Recent evidence has demonstrated that neural expiration may be divided into two phases. A critical role in defining these phases is exercised by the discharge of post-inspiratory neurons. However, information concerning these neuronal activities is conflicting. This conflicting information may reflect the existence of subpopulations. The hypothesis will be evaluated that some post-inspiratory neurons are premotor to pharyngeal or laryngeal motoneurons whereas others are involved in the definition of expiratory activity for the entire ventilatory control system. The final studies will characterize a neuronal circuit which is critical only for expiratory activities of spinal nerves. This circuit, involving the infracerebellar nucleus of the cerebellum, is hypothesized to regulate spinal motonueronal activities by a pathway which bypasses the medullary respiratory nuclei. Activity within this circuit may provide an explanation for several enigmas concerning the regulation of spinal expiratory activities, including the influence of posture and the elimination of these activities, but not those of bulbospinal expiratory neurons, in anesthesia.