Central and peripheral chemoreceptors evoke distinct responses in simultaneously recorded neurons of the raphé-pontomedullary respiratory network

Abstract

The brainstem network for generating and modulating the respiratory motor pattern includes neurons of the medullary ventrolateral respiratory column (VRC), dorsolateral pons (PRG) and raphé nuclei. Midline raphé neurons are proposed to be elements of a distributed brainstem system of central chemoreceptors, as well as modulators of central chemoreceptors at other sites, including the retrotrapezoid nucleus. Stimulation of the raphé system or peripheral chemoreceptors can induce a long-term facilitation of phrenic nerve activity; central chemoreceptor stimulation does not. The network mechanisms through which each class of chemoreceptor differentially influences breathing are poorly understood. Microelectrode arrays were used to monitor sets of spike trains from 114 PRG, 198 VRC and 166 midline neurons in six decerebrate vagotomized cats; 356 were recorded during sequential stimulation of both receptor classes via brief CO 2 -saturated saline injections in vertebral (central) and carotid arteries (peripheral). Seventy neurons responded to both stimuli. More neurons were responsive only to peripheral challenges than those responsive only to central chemoreceptor stimulation (PRG, 20 : 4; VRC, 41 : 10; midline, 25 : 13). Of 16 474 pairs of neurons evaluated for short-time scale correlations, similar percentages of reference neurons in each brain region had correlation features indicative of a specific interaction with at least one target neuron: PRG (59.6%), VRC (51.0%) and raphé nuclei (45.8%). The results suggest a brainstem network architecture with connectivity that shapes the respiratory motor pattern via overlapping circuits that modulate central and peripheral chemoreceptor-mediated influences on breathing.

Arousal from sleep in response to intermittent hypoxia in rat pups is modulated by medullary raphe GABAergic mechanisms

“…Some of these pathways are likely components of the raphe-ponto-medullary network referred to above. Further, the effects of hypoxia on sympathetic outflow to brown fat might involve inhibition of presympathetic neurons in the medullary raphe by GABAergic projections from the com NTS (53,58). These data all suggest that neurons in the medullary raphe are activated during peripheral chemoreceptor stimulation.…”

“…Stimulation of the carotid sinus nerves induces c-Fos-like protein in regions of the medullary raphe (23). Multiarray extracellular recordings further suggest that midline raphe neurons are critical components of a larger raphe-ponto-medullary network of neurons with respiratory related activity and respond to peripheral chemoreceptor stimulation in concert with the entire network (58). Although there is clear evidence of direct projections of medullary raphe 5-HT neurons to the NTS (69), the existence of direct projections from the com NTS to the medullary raphe is less clear.…”

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

“…Peripheral chemoreceptors of the carotid body rapidly sense changes in arterial O 2 and CO 2 -pH and also modulate the drive to breathe (Kumar and Prabhakar 2012), although the functional connections through which they act upon VRC circuits remain incompletely understood (Nuding et al 2009b;Spyer and Gourine 2009). Having previously identified differential peripheral chemoreceptor modulation of inspiratory neurons in the pre-Bötzinger region and more caudal medullary domains (Morris et al 1996(Morris et al , 2001), we had the second objective of testing the hypothesis that carotid chemoreceptors enhance inspiratory drive via downstream disinhibitory actions of t-E neurons upon caudal columnar inspiratory neurons.…”

Brainstem: neural networks vital for life

“…How prevalent are chemically and electrically mediated synaptic transmission and what transmitters are used (Cifra et al 2009)? Related problems concern whether multiple sites for rhythm generation exist, and if so how many there are and where they are situated in the pons and/or medulla (Nuding et al 2009;Smith et al 2009;St John 2009).…”

“…Thus, for the first time, it has now become possible to record the activity of large numbers of neurons simultaneously by multi-electrode arrays (Nuding et al 2009) and by optical methods, without electrodes (Champagnat et al 2009;Homma et al 2009;Muller et al 2009;Smith et al 2009). Inevitably, when one records from vast numbers of cells at once, complexities arise in both analysis and interpretation that require sophisticated computational programmes (Nuding et al 2009;Smith et al 2009). In addition, several new preparations have been devised in which one can make use of these techniques, including slices, isolated brainstems, intraarterially perfused in situ and intact anaesthetized animals.…”