Modulation of gasp frequency by activation of pre-Botzinger complex in vivo

Under hyperoxic conditions, both chemical stimulation of neurons and focal hypoxia in the pre-Botzinger complex (pre-BotC) in vivo modify the eupneic pattern of inspiratory motor output by eliciting changes in the patterning and timing of phrenic bursts, which includes both phasic and tonic excitation. The influence of this region on the gasping pattern of phrenic motor output produced during severe brain hypoxia is unknown. We therefore examined the effects of chemical stimulation of neurons (DL-homocysteic acid; DLH; 10 mM; less than or equal to20 nl) and focal hypoxia (sodium cyanide; NaCN; 1 mM; less than or equal to20 nl) in the pre-BotC on hypoxia-induced gasping in chloralose-anesthetized, vagotomized, mechanically ventilated cats. Unilateral microinjection of DLH into the pre-BotC during hypoxia-induced gasping increased phrenic burst frequency by similar to630% (P<0.01) over baseline frequency due predominantly to a reduction in T-E (from 28.9&PLUSMN;6.2 to 5.2&PLUSMN;1.8 s; mean &PLUSMN; SE; P<0.01). No significant changes in T-I or rate of rise between hypoxia-induced gasps and the DLH-induced bursts were observed; the effects on peak amplitude of integrated phrenic nerve discharge were variable. Similar responses were evoked by unilateral microinjection of NaCN into the pre-BotC. These findings demonstrate that both activation of pre-BotC neurons and focal hypoxia in the pre-BotC not only influence the eupneic pattern of phrenic motor output but also modify the expression of hypoxia-induced gasping in vivo. These findings also provide additional support to the concept of intrinsic hypoxic chemosensitivity of the pre-BotC.