The overall goal of our research is to explain the behavior of the respiratory control system based upon a neurophysiologic and neuroanatomic understanding of individual neuronal elements and their interconnections. One major thrust of this proposal is to understand how the brain stem integrates sensory inputs from two classes of pulmonary receptors--the slowly adapting pulmonary stretch receptors (PSRs) and the rapidly adapting pulmonary stretch receptors (RARs). Inputs from both of these receptor classes have profound effects upon respiratory rhythm. The first specific aim is to complete our preliminary studies utilizing intracellular spike-triggered averaging to determine the synaptic relationships between these two types of afferents and individual dorsal respiratory group (DRG) neurons in the dorsomedial medulla. The second specific aim is to inject the enzyme horseradish peroxidase (HRP) into the central axons of single PSRs and RARs to study their projections and terminations within the solitary tract region of the medulla. The third specific aim is to investigate the neural connections between DRG P-cells, the key interneurons for PSR inputs, and nearby DRG inspiratory cells using the methodology of cross-correlational analysis. The fourth specific aim is to determine the morphology of P-cells using intracellular application of HRP. Another major thrust of our research is to utilize the intracellular application of HRP to determine the morphology of other neuronal elements involved in the brain stem regulation of breathing. To do this our fifth specific aim involves determining the morphology of the diverse population of neurons that comprise the ventral respiratory group (VRG) in the ventrolateral medulla. The sixth specific aim is to intraxonally inject HRP into bulbospinal respiratory axons in the cervical cord to determine their axonal trajectories, collateralization and terminals in the phrenic motor nucleus. The results from these projects focused upon medullary control of breathing and utilizing two diverse methodologies, one neurophysiologic and the other neuroanatomic, should provide new and important understandings of the normal functioning of the central nervous system in respiration.
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