Respiratory and Mayer Wave-Related Discharge Patterns of Raphé and Pontine Neurons Change With Vagotomy

Document Type

Article

Publication Date

2010

Keywords

pons, breathing, respiratory motor pattern

Digital Object Identifier (DOI)

https://doi.org/10.1152/japplphysiol.01324.2009

Abstract

Previous models have attributed changes in respiratory modulation of pontine neurons after vagotomy to a loss of pulmonary stretch receptor “gating” of an efference copy of inspiratory drive. Recently, our group confirmed that pontine neurons change firing patterns and become more respiratory modulated after vagotomy, although average peak and mean firing rates of the sample did not increase (Dick et al., J Physiol 586: 4265–4282, 2008). Because raphé neurons are also elements of the brain stem respiratory network, we tested the hypotheses that after vagotomy raphé neurons have increased respiratory modulation and that alterations in their firing patterns are similar to those seen for pontine neurons during withheld lung inflation. Raphé and pontine neurons were recorded simultaneously before and after vagotomy in decerebrated cats. Before vagotomy, 14% of 95 raphé neurons had increased activity during single respiratory cycles prolonged by withholding lung inflation; 13% exhibited decreased activity. After vagotomy, the average index of respiratory modulation (η2) increased (0.05 ± 0.10 to 0.12 ± 0.18 SD; Student's paired t-test, P < 0.01). Time series and frequency domain analyses identified pontine and raphé neuron firing rate modulations with a 0.1-Hz rhythm coherent with blood pressure Mayer waves. These “Mayer wave-related oscillations” (MWROs) were coupled with central respiratory drive and became synchronized with the central respiratory rhythm after vagotomy (7 of 10 animals). Cross-correlation analysis identified functional connectivity in 52 of 360 pairs of neurons with MWROs. Collectively, the results suggest that a distributed network participates in the generation of MWROs and in the coordination of respiratory and vasomotor rhythms.

brain stem network mechanisms have essential roles in the control and coordination of cardiovascular and respiratory functions (cardiorespiratory coupling) (86). It is well established that sympathetic nerve activity can burst rhythmically with respiration and that this activity is modulated by sensory feedback and physiological state (1, 31, 45, 56, 75, 93, 95). Recently, we demonstrated the reciprocal relationship: respiratory activity is modulated with arterial pulse (25, 26). Although it has been known for some time that baroreceptor feedback influences the drive to breathe (4, 5, 14, 19, 20, 33, 35, 96), this new result suggests that the detailed activity patterns of respiratory premotoneurons and motoneurons are also pulse pressure modulated on a beat-by-beat basis.

The dorsolateral (dl) pons, which includes the pontine respiratory group, is an important brain region for respiratory pattern generation and the modulation of breathing and cardiovascular activity (15, 37, 46, 72, 83, 84). Withholding lung inflation during a respiratory cycle in neuromuscularly blocked, thoracotomized, decerebrated cats alters the strength and consistency of respiratory-modulated activity in some pontine neurons (15, 83). Similar results have been observed after vagotomy (10). It has been proposed that these altered discharge patterns reflect a loss of phasic lung volume feedback and stretch receptor-driven presynaptic inhibition or “gating” of an efference copy of inspiratory drive and provide a feedback inhibition that enhances intrinsic inspiratory-to-expiratory phase switching mechanisms (15).

We recently tested the hypothesis that dl pontine neuron activity patterns during a “delayed-inflation” test (similar to no-inflation tests during neural inspiration) would be comparable to those shown after vagotomy (27). Using multisite recording methods, we compared concurrent changes in the respiratory-modulated firing rates of pontine respiratory group neurons. Overall, changes in activity patterns during the delayed-inflation test cycles were similar to those after vagotomy, with notable exceptions at the phase transition from inspiration to expiration. We also recorded neurons that were functionally excited by lung inflation and neurons with firing rate changes that persisted longer than the delayed-inflation cycle.

Raphé neurons modulate sympathetic nerve activity (6, 7, 16, 32, 48, 55, 69, 87, 90). Medullary raphé neurons are integral elements of the brain stem respiratory network (71); caudal raphé networks have been postulated to provide dynamic gain control for the brain stem respiratory network (50, 52, 63–65). However, the afferent inputs and efferent projections of raphé neurons and their roles in cardiorespiratory control are not well understood. Because of the apparent overlap in action, we hypothesized that the caudal raphé neurons may have properties similar to dl pontine neurons.

In the course of the aforementioned pontine neuron recordings, we also monitored medullary raphé neuron activity as part of a larger study on the network mechanisms for cardiorespiratory coupling. We report here that the respiratory-modulated firing rates and discharge patterns of many raphé neurons were altered much like the pontine neurons both during delayed-inflation tests and after vagotomy, suggesting coordinated pontine-raphé network mechanisms for brain stem cardiorespiratory coupling.

Cherniack et al. (12), recording only the blood pressures and phrenic nerve activities of anesthetized, neuromuscularly blocked dogs, observed that “Maneuvers (vagotomy or arrested ventilation) which slowed the bursts of phrenic nerve activity and increased the electrical activity of each burst converted Mayer to Traube-Hering waves.” Traube-Hering waves in arterial blood pressure are associated with central respiratory drive, whereas Mayer waves are oscillations of arterial pressure of around 0.1 Hz, typically slower than respiration. Mayer waves historically have been attributed to a central oscillator or characterized as a resonant frequency of the baroreceptor reflex (for review, see Ref. 40). More recently, a “pervasive” 0.1-Hz oscillation in reflected light observed during neural imaging studies has been associated with regional cerebral blood flow (54), and neurons in the caudal raphé nuclei and ventrolateral medulla of sinoaortic denervated cats were found to have oscillations that were coherent with Mayer waves (58, 59, 77).

Using multi-electrode arrays to record raphé and pontine neuron spike trains simultaneously, we identified firing rate oscillations modulated with the respiratory rhythm, the heartbeat, and Mayer waves. Coupling of the respiratory rhythm and Mayer wave-related oscillations (MWROs) was altered by delayed lung inflation and vagotomy. Short time scale correlations indicative of paucisynaptic interactions between raphé and pontine neurons with MWROs were also detected. Collectively, the results suggest that a distributed network participates in the generation of MWROs and coordination of respiratory and vasomotor rhythms.

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Citation / Publisher Attribution

Journal of Applied Physiology, v. 109, issue 1, p. 189-202

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