Medullary raphe neurones and baroreceptor modulation of the respiratory motor pattern in the cat

Abstract

Perturbations of arterial blood pressure change medullary raphe neurone activity and the respiratory motor pattern. This study sought evidence for actions of baroresponsive raphe neurones on the medullary respiratory network. Blood pressure was perturbed by intravenous injection of an α1‐adrenergic receptor agonist, unilateral pressure changes in the carotid sinus, or occlusion of the descending aorta in thirty‐six Dial‐urethane‐anaesthetized, vagotomized, paralysed, artificially ventilated cats. Neurones were monitored with microelectrode arrays in two or three of the following domains: nucleus raphe obscurus‐nucleus raphe pallidus, nucleus raphe magnus, and rostral and caudal ventrolateral medulla. Data were analysed with cycle‐triggered histograms, peristimulus time and cumulative sum histograms, cross‐correlograms and spike‐triggered averages of efferent phrenic nerve activity. Prolongation of the expiratory phase and decreased peak integrated phrenic amplitude were most frequently observed. Of 707 neurones studied, 310 had altered firing rates during stimulation; changes in opposite directions were monitored simultaneously in fifty‐six of eighty‐seven data sets with at least two baroresponsive neurones. Short time scale correlations were detected between neurones in 347 of 3388 pairs. Seventeen pairs of baroresponsive raphe neurones exhibited significant offset correlogram features indicative of paucisynaptic interactions. In correlated raphe‐ventrolateral medullary neurone pairs with at least one baroresponsive neurone, six of seven ventrolateral medullary decrementing expiratory (E‐Decr) neurones increased their firing rate during baroreceptor stimulation. Thirteen of fifteen ventrolateral medullary inspiratory neurones correlated with raphe cells decreased their firing rate during baroreceptor stimulation. The results support the hypothesis that raphe neuronal assemblies transform and transmit information from baroreceptors to neurones in the ventral respiratory group. The inferred actions both limit and promote responses to sensory perturbations and match predictions from simulations of the respiratory network.

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

“…Short-timescale correlations of t-E neuron spike trains identified with cross-correlation confirmed the presence of coordinated clusters of t-E neurons within the VRC. Complementary gravity clustering methods revealed fluctuations in firing synchrony that presumably reflect actions of shared influences, including functional connections identified in this study and previously (Lindsey et al 1998;Nuding et al 2009aNuding et al , 2009bOtt et al 2012). Both methods also detected evidence of inhibitory actions of chemoresponsive t-E neurons on inspiratory neurons, results consistent with roles in gain modulation circuits for adjustment of inspiratory drive.…”

“…More generally, decreased activity of t-E neurons during inspiration may operate to counterbalance the suppressive influence of increased arterial blood pressure on inspiratory drive due to excitation and disinhibition of t-E activity (Fig. 8B, 5) via raphé circuits during chemoreceptorand cough-evoked increases in blood pressure (Lindsey et al 1998;Poliaček et al 2011).…”

“…First, baroreceptor-evoked reductions in inspiratory drive are associated with increased firing rates in t-E neurons that have inhibitory functional connections with inspiratory premotor or motor neurons (Lindsey et al 1998). Second, central chemoreceptor-evoked enhancement of inspiratory drive occurs during suppressed inspiratory-phase activity in t-E neurons (Ott et al 2012).…”

Arterial pulse modulated activity is expressed in respiratory neural output

“…On the other hand, the modulatory influence of cardiovascular parameters on respiratory neuronal activity has not been widely recognized, despite numerous reports concerning barorespiratory reflexes (7,13,19,21,22,25,28,29,32,36,38,40) and the known modulatory effects of baroreceptor stimulation on medullary respiratory activity (2,9,17,21,22,25,32). The barorespiratory reflex has been described as acute increases in blood pressure leading to decreased respiratory frequency and tidal volume (8,13,19,29).…”

Subtype Composition and Responses of Respiratory Neurons in the Pre-Bötzinger Region to Pulmonary Afferent Inputs in Dogs

“…The response characteristics of pre-BC neurons to systematic changes in phase timing produced by pulmonary afferent inputs have received limited attention (Hayashi et al 1996), although reflexly induced changes in phase timing and neuronal responses to peripheral chemoreceptor (Morris et al 1996), baroreceptor (Lindsey et al 1998), and airway defense receptor (Shannon et al 2000) stimulation have been studied. The discharge patterns of those neurons that play a key role in generation and control of phase timing should exhibit some aspect of their pattern that is consistently related to TI or TE.…”