Our hypotheses are that excitatory amino acids (EAA) play a major role in CNS control of cardiorespiratory function, and that derangements in EAA neurotransmission could result in cardiorespiratory disorders. We will test these hypotheses in anesthetized animals as well as in decerebrate animals by: 1) determining the role of EAA in tonic, CNS control, and in reflex and chemical control of cardiorespiratory activity by microinjecting either specific antagonists of EAA, EAA or drugs that inhibit the uptake of EAA into nerve terminals, into specific nuclei in the CNS circuitry controlling cardiorespiratory function while monitoring indices of cardiorespiratory activity; 2) determining whether alterations in the allosteric modulatory center influencing the N-methyl-D-aspartate (NMDA) receptor will alter cardiorespiratory activity; 3) using the intermediolateral cell column, the phrenic motor nucleus and the spinal cord nuclei containing motorneurons for the intercostal muscles; 4) using immunohistochemical cardiorespiratory activity, and to use immunohistochemistry combined with anterograde and retrograde tracing techniques to determine the origin and/or termination of these neurons;5) determining functional interactions between excitatory amino acid containing neurons and other neurotransmitter containing neurons controlling cardiorespiratory activity; and 6) beginning to use the information obtained by studies described in (1) through (5) to determine the role of EAA in causing derangements in cardiorespiratory function such as hypertension, obstructive sleep apnea and acute respiratory failure. As yet, EAA have not been implicated in derangements of cardiorespiratory function. However, because preliminary data indicate that EAA influence sites where the heaviest neural traffic enters and exits the CNS, and that the non-competitive NMDA antagonist, MK801, produces profound changes in cardiorespiratory function, it is clear that a study of EAA in CNS cardiorespiratory function will advance current knowledge in how the CNS controls cardiorespiratory function.
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