MECHANISMS AND SITES OF VENTILATORY NEUROGENESIS

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DESCRIPTION (Adapted from the applicant's abstract): The automatic ventilatory patterns of eupnea and gasping can be observed from the day of birth. In eupnea and gasping, the discharge patterns of neuronal and neural activities are fundamentally different. In adult rats and cats, a medullary region has been identified which is critical for the neurogenesis of gasping, but not eupnea. This "gasping center" partially overlaps with regions, termed the "pre-Botzinger" complex and "Pre-I" region, which are reported to contain neurons whose discharge underlies rhythm generation in an in vitro preparation of the neonatal rat. The "gasping center", "pre-Botzinger" complex and "Pre- I" region may represent a continuous functional unit. This hypothesis is supported by the identity of the rhythmic activity of the in vitro preparation with gasping of in vivo neonatal rats. Moreover, in these neonatal animals, destruction of neurons in the various medullary regions eliminates gasping, but does not alter eupnea. The roles of medullary neuronal activities in the neurogenesis of eupnea and gasping will be assessed. The mechanisms will be evaluated by which these medullary neuronal activities underlying gasping are suppressed in eupnea. Specifically, the discharge of pontile neuronal activities is considered as the source of this suppression. In eupnea, pharmacological "disinhibition" and/or excitation of medullary neuronal activities should result in gasping. The studies proposed will define the mechanisms whereby the dominance of the eupneic ventilatory rhythm is established. Results will provide a basis for understanding the failure of mechanisms for ventilatory neurogenesis, in apneas of neonates and adults.