Progressive brain hypoxia in a glomectomized, vagotomized cat results in stereotyped changes in the patterning of the phrenic neurogram. Initial depression of phrenic amplitude progresses to apnea and gasping as the severity of hypoxia increases. Gasping apparently serves as a means of """"""""autoresuscitation"""""""" and improves survival of animals, particularly neonates, if ambient oxygen is restored. The main premise of this proposal is that gasping results from a selective hypoxic depression of pontine structures which normally inhibit a medullary gasping pattern generator. Three specific hypotheses will be tested: 1) The brainstem has a rostral-to-caudal gradient of hypoxic vulnerability. The applicant will compare the hypoxic response of pontile and medullary respiratory outputs and measure extracellular [K+] in both brain regions as an index of normal cellular function. To determine if selective vulnerability results from a rostral-to-caudal gradient of tissue hypoxia, tissue oxygenation will be measured in pons and medulla during hypoxia. 2) The medullary gasping pattern generator is inhibited during normoxia and disinhibited during hypoxia. These studies will test the ability of the inhibitory neurotransmitters, gamma-aminobutyric acid (GABA) and glycine, and their antagonists to modify gasping following microinjection into the medullary gasping center. The applicant will test the ability of GABA and glycine to abolish hypoxic gasping following injection into this medullary site. Bicuculline and strychnine, antagonists of GABA and glycine respectively, will be tested for their ability to produce gasping in normoxic animals following medullary microinjection. 3) Hypoxic gasping results from disinhibition of medullary gasping pattern generator by the pons. This hypothesis will be tested by determining whether electrical and chemical stimulation of the pontine reticular formation inhibits hypoxic gasping. Since inhibitory neurotransmitters are known to contribute to neuronal depression during hypoxia, antagonists of GABA and glycine will be microinjected into the pontine reticular formation during hypoxia to test whether reversal of pontine inhibition will inhibition hypoxic gasping.
