Ventrolateral medullary functional connectivity and the respiratory and central chemoreceptor-evoked modulation of retrotrapezoid-parafacial neurons

Abstract

The medullary ventral respiratory column (VRC) of neurons is essential for respiratory motor pattern generation; however, the functional connections among these cells are not well understood. A rostral extension of the VRC, including the retrotrapezoid nucleus/parafacial region (RTN-pF), contains neurons responsive to local perturbations of CO(2)/pH. We addressed the hypothesis that both local RTN-pF interactions and functional connections from more caudal VRC compartments--extending from the Bötzinger and pre-Bötzinger complexes to the ventral respiratory group (Böt-VRG)--influence the respiratory modulation of RTN-pF neurons and their responses to central chemoreceptor and baroreflex activation. Spike trains from 294 RTN-pF and 490 Böt-VRG neurons were monitored with multielectrode arrays along with phrenic nerve activity in 14 decerebrate, vagotomized cats. Overall, 214 RTN-pF and 398 Böt-VRG neurons were respiratory modulated; 124 and 95, respectively, were cardiac modulated. Subsets of these neurons were tested with sequential, selective, transient stimulation of central chemoreceptors and arterial baroreceptors; each cell's response was evaluated and categorized according to the change in firing rate (if any) following the stimulus. Cross-correlation analysis was applied to 2,884 RTN-pF↔RTN-pF and 8,490 Böt-VRG↔RTN-pF neuron pairs. In total, 174 RTN-pF neurons (59.5%) had significant features in short-time scale correlations with other RTN-pF neurons. Of these, 49 neurons triggered cross-correlograms with offset peaks or troughs (n = 99) indicative of paucisynaptic excitation or inhibition of the target. Forty-nine Böt-VRG neurons (10.0%) were triggers in 74 Böt-VRG→RTN-pF correlograms with offset features, suggesting that Böt-VRG trigger neurons influence RTN-pF target neurons. The results support the hypothesis that local RTN-pF neuron interactions and inputs from Böt-VRG neurons jointly contribute to respiratory modulation of RTN-pF neuronal discharge patterns and promotion or limitation of their responses to central chemoreceptor and baroreceptor stimulation.

Brainstem mechanisms underlying the cough reflex and its regulation

“…Oku et al, 1994;Bongianni et al, 1998;Shannon et al, 1996;Bolser and Davenport 2002;Pantaleo et al, 2002;Baekey et al, 2003;Ott et al, 2011). These findings support the existence of multifunctional neural networks in the mammalian brainstem and, accordingly, of neurons that contribute to different functions, such as respiration, coughing, vomiting and sneezing.…”

Peripheral chemoreceptors tune inspiratory drive via tonic expiratory neuron hubs in the medullary ventral respiratory column network

“…Data were obtained from 22 adult cats (2.8 -5.6 kg) of either sex, and descriptions of most methods have been published previously (Nuding et al 2009b;Ott et al 2011). Animals were initially anesthetized with isoflurane (3-5%) or with ketamine hydrochloride (5.5 mg/kg im) followed by isoflurane; all were maintained with 0.5-3.0% isoflurane until decerebration (Kirsten and St. John 1978).…”

Role of the dorsal medulla in the neurogenesis of airway protection

“…This computational model has been informed by a variety of different studies, including the results of multi-electrode recordings from brainstem neurons that participate in cough, swallow, and breathing [19, 21, 22, 24, 35–49]. These recordings of neuronal spike trains have been analyzed with a variety of methods intended to provide information regarding functional connectivity between neurons.…”