Patterns of Phrenic Motor Output Evoked by Chemical Stimulation of Neurons Located in the Pre-Bötzinger Complex In Vivo

Abstract

The pre-Bötzinger complex (pre-BötC) has been proposed to be essential for respiratory rhythm generation from work in vitro. Much less, however, is known about its role in the generation and modulation of respiratory rhythm in vivo. Therefore we examined whether chemical stimulation of the in vivo pre-BötC manifests respiratory modulation consistent with a respiratory rhythm generator. In chloralose- or chloralose/urethan-anesthetized, vagotomized cats, we recorded phrenic nerve discharge and arterial blood pressure in response to chemical stimulation of neurons located in the pre-BötC with DL-homocysteic acid (DLH; 10 mM; 21 nl). In 115 of the 122 sites examined in the pre-BötC, unilateral microinjection of DLH produced an increase in phrenic nerve discharge that was characterized by one of the following changes in cycle timing and pattern: 1) a rapid series of high-amplitude, rapid rate of rise, short-duration bursts, 2) tonic excitation (with or without respiratory oscillations), 3) an integration of the first two types of responses (i.e., tonic excitation with high-amplitude, short-duration bursts superimposed), or 4) augmented bursts in the phrenic neurogram (i.e., eupneic breath ending with a high-amplitude, short-duration burst). In 107 of these sites, the phrenic neurogram response was accompanied by an increase or decrease (>/=10 mmHg) in arterial blood pressure. Thus increases in respiratory burst frequency and production of tonic discharge of inspiratory output, both of which have been seen in vitro, as well as modulation of burst pattern can be produced by local perturbations of excitatory amino acid neurotransmission in the pre-BötC in vivo. These findings are consistent with the proposed role of this region as the locus for respiratory rhythm generation.

Focal acidosis in the pre-Bötzinger complex area of awake goats induces a mild tachypnea

“…Second, a FA in the preBötzC does not elicit nonrespiratory effects, whereas a FA in the MRN (10,11) or CFN (17) results in significant changes in V O 2 , MABP, or HR. These first two unique effects seem consistent with the important role of the preBötzC in respiratory rhythm generation (4,19,23,29,30,37). Third, bilateral FA with 25 and 50% CO 2 in the preBötzC does not elicit any consistent or significant ventilatory response, whereas bilateral FA in the MRN elicits a greater response than a unilateral FA (10,11).…”

“…Physiologically, the preBötzC can be defined by a distinct, unique tachypnic and dysrhythmic response to injection of a glutamate receptor agonist (19,30,37). Weeks after the completion of the FA studies, the glutamate agonist IA was injected into the preBötzC in incremental volumes over a period of 4 wk.…”

“…A glutamate receptor agonist applied to the preBötzC elicits a classic physiological response, manifested as an increase in f (19,30,37). Weeks after the completion of the FA studies, the neurotoxin ibotenic acid (IA), an irreversible glutamate receptor agonist, was injected into the preBötzC of the present group of goats to examine the plasticity of respiratory rhythmogenesis.…”

“…This relatively small response to FA might, in part, be due to alkalosis at other chemosensitive sites during FA at one or a few sites. Accordingly, it is conceivable that the hyperpnea during global brain acidosis reflects the cumulative or additive effect of chemoreception at multiple sites, rather than a result of activation of chemoreceptors at any single site.The preBötzC, a medullary area hypothesized to be the dominant inspiratory rhythm generator (4,19,23,29,30,37), may also contain neurons that exhibit CO 2 /H ϩ sensitivity. Notably, an acetazolamide-induced acidosis in the preBötzC of anesthetized, vagotomized, paralyzed, and mechanically ventilated cats increases the frequency and amplitude of phrenic nerve activity (31, 32).…”

“…The preBötzC, a medullary area hypothesized to be the dominant inspiratory rhythm generator (4,19,23,29,30,37), may also contain neurons that exhibit CO 2 /H ϩ sensitivity. Notably, an acetazolamide-induced acidosis in the preBötzC of anesthetized, vagotomized, paralyzed, and mechanically ventilated cats increases the frequency and amplitude of phrenic nerve activity (31,32).…”