Role of the pre-Bötzinger complex in respiratory rhythm generation in vivo: influence of respiratory network drive

IC Solomon

doi:10.1186/rr95

Abstract

We have previously demonstrated that microinjection of DL-homocysteic acid (DLH), a glutamate analog, into the pre-Botzinger complex (pre-BotC) can produce either phasic or tonic excitation of phrenic nerve discharge. Our initial findings were obtained during hyperoxic normocapnia; thus, the influence of respiratory network drive, including intrinsic pre-BotC neuronal excitability, on the DLH-induced modulation of phrenic motor output requires clarification. We, therefore, examined the effects of chemical stimulation of the pre-BotC during increased respiratory network drive elicited by hypercapnia, hypoxia (ie, peripheral chemoreflex), or focal pre-BotC tissue acidosis in chloralose-anesthetized, vagotomized, mechanically ventilated cats. For these experiments, we selected sites in which unilateral microinjection of DLH into the pre-BotC during hyperoxic normocapnia (PaCO2 = 37–43 mmHg) produced a non-rhythmic tonic excitation of phrenic nerve discharge. During hypercapnia (PaCO2 = 59.7 ± 2.8 mmHg; n = 17), similar microinjection produced excitation in which respiratory rhythmic oscillations were superimposed on varying levels of tonic discharge. A similar pattern of modulation was observed in response to microinjection of DLH into the pre-BotC during normocapnic hypoxia (PaCO2 = 38.5 ± 3.7; PaO2 = 38.4 ± 4.4; n = 8) and during focal pre-BotC tissue acidosis (n = 7). Further, during increased respiratory network drive, these DLH-induced respiratory rhythmic oscillations had an increased frequency compared to the preinjection baseline frequency of phrenic bursts (P < 0.05). These findings demonstrate that tonic inspiratory motor activity evoked by chemical stimulation of the pre-BotC is influenced by and integrates with modulation of respiratory network drive mediated by input from both central and peripheral chemoreceptors, as well as focal pre-BotC CO2/H+ chemosensitivity.

Highlights

To be effective, inspiratory muscles on the left and right sides must contract together
We have found that a prominent gap in the column of ventral respiratory group (VRG) The nucleus tractus solitarii (NTS) relays information from primary related parvalbumin cells [2] likely corresponds to the pBc since visceral receptors to the central nervous system and is critically parvalbumin cells are rare in this zone and never co-localize with involved in the reflex control of autonomic functions
The specific protein(s) necessary for longterm facilitation (LTF) is unknown, we recently found that episodic hypoxia and LTF are associated with elevations in ventral spinal concentrations of brain derived neurotrophic factor (BDNF)

Summary

Introduction

Inspiratory muscles on the left and right sides must contract together. The left and right halves of the diaphragm are synchronised because a bilateral population of medullary premotor neurones [1] simultaneously excites left and right phrenic motoneurones. Transection studies demonstrate that each side of the brainstem is capable of generating respiratory rhythm independently [2], so that left and right medullary inspiratory neurones must themselves be synchronised. The interconnections and common excitation that accomplish such synchronisation are unknown in rats. The respiratory rhythm of hypoglossal (XII) nerve discharge in transverse medullary slice preparations from neonatal rats is thought to originate in the region of the ventral respiratory group (VRG); generated there by a combination of “pacemaker” neurones [1] and their interactions with other respiratory neurones. Our goal was to discover interconnections between left and right VRG neurones as well as their connections to XII motoneurones

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