HYPOTHALAMIC GABAERGIC MODULATION OF RESPIRATORY RESPONSES TO BARORECEPTOR STIMULATION

Little is known about possible hypothalamic modulation of the respiratory response to baroreceptor activation. The purpose of this study was to determine if the respiratory depression associated with the baroreceptor reflex is modulated by neurons in the posterior hypothalamus. Breathing frequency and tidal diaphragmatic activity were derived from diaphragmatic electromyographic recordings in anesthetized rats. Respiratory responses to baroreceptor activation were analyzed before and after unilateral microinjections of GABA antagonists (picrotoxin, bicuculline methiodide) or a GABA synthesis inhibitor (3-mercaptopropionic acid, 3-MP) into the posterior hypothalamus. Baroreceptor stimulation prior to microinjections elicited a decrease in both breathing frequency and tidal diaphragmatic activity. Microinjection of picrotoxin elicited an increase in respiratory activity. The decrease in tidal diaphragmatic activity evoked by baroreceptor stimulation was blocked after the microinjection. Furthermore, the baroreceptor-induced fall in breathing frequency was converted to an increase in breathing frequency. These effects of picrotoxin were reversed by microinjections of a GABA agonist (muscimol) into the same site. Microinjection of 3-MP also blocked the decrease in breathing frequency associated with baroreceptor stimulation. The GABA antagonist bicuculline methiodide elicited similar effects. These results indicate that a GABAergic mechanism in the posterior hypothalamus modulates the respiratory responses to baroreceptor stimulation.