Posterior hypothalamic modulation of the respiratory response to CO2 in cats

Several studies have provided evidence that suprapontine structures are involved in modulating the respiratory response to increases in carbon dioxide. However, the actual neuroanatomical site(s) responsible for this effect has not been identified. Therefore, the purpose of the present study was to determine if the posterior hypothalamus is one rostral site involved in the modulation of the respiratory response to hypercapnia. Phrenic nerve responses to progressive step increases in end-tidal PCO2 were recorded before and after unilateral microinjection of gamma-aminobutyric acid (GABA) antagonists into the posterior hypothalamus of anesthetized cats, which were paralyzed and ventilated. Microinjection of the antagonists reduced the apneic threshold to lower values of end-tidal PCO2. In addition, phrenic nerve responses to changes in CO2 above the apneic threshold were augmented following microinjections of the GABA antagonists. This augmentation resulted from larger respiratory frequency responses with slight increases in the tidal phrenic response. Microinjection of a GABA agonist into the same hypothalamic site reversed the effects of the GABA antagonist. Microinjection of the GABA agonist without a preceding antagonist injection had no effects. These results suggest that the respiratory responses to increases in PCO2 above the apneic threshold are modulated by neurons in the posterior hypothalamus in anesthetized cats. This hypothalamic modulation involves a GABAergic mechanism.