The purpose of the research in this proposal is to investigate hypothalamic involvement in the control of the respiratory system. Several studies have demonstrated that areas in the hypothalamus are involved in modulating some cardiovascular reflexes. For example, the cardiovascular responses to stimulation of baroreceptors and peripheral chemoreceptors are known to be modified by sites in the hypothalamus. Even though activation of these receptors also affects ventilation, almost no research has examined a role of the hypothalamus in regulating respiratory responses. Therefore, the specific aims of the studies described in this proposal are to investigate a potential role of hypothalamic sites in regulating respiratory reflexes and to determine the neurotransmitters utilized by the hypothalamic sites which modulate breathing. The respiratory reflexes to be studied are those evoked by stimulation of 1) pulmonary stretch receptors (Hering-Breuer reflex); 2) peripheral chemoreceptors; 3) central chemoreceptors and 4) arterial baroreceptors. Three sets of experiments will be performed in anesthetized cats. First, the effects of changing the """"""""excitability state"""""""" of neurons in selected hypothalamic sites upon the respiratory reflexes will be determined. The excitability state will be raised by chemical or electrical stimulation and will be lowered by electrolytic lesions or by focal cooling of hypothalamic sites. In a second set of experiments the effects upon the respiratory reflexes of microinjecting neurotransmitter antogonists into the hypothalamus will be evaluated. Finally, it will be determined if the respiratory stimuli listed above alter the discharge frequency of hypothalamic neurons. The information gained from these experiments should add to the overall understanding of the neural control of respiration. These findings may offer insights into the neurological abnormalities responsible for some central respiratory disorders.
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