Blood pressure drives multispectral tuning of inspiration via a linked-loop neural network

Abstract

The respiratory motor pattern is coordinated with cardiovascular system regulation. Inspiratory drive and respiratory phase durations are tuned by blood pressure and baroreceptor reflexes. We hypothesized that perturbations of systemic arterial blood pressure modulate inspiratory drive through a raphe-pontomedullary network. In 15 adult decerebrate vagotomized neuromuscular-blocked cats, we used multielectrode arrays to record the activities of 704 neurons within the medullary ventral respiratory column, pons, and raphe areas during baroreceptor-evoked perturbations of breathing, as measured by altered peak activity in integrated efferent phrenic nerve activity and changes in respiratory phase durations. Blood pressure was transiently (30 sec.) elevated or reduced by inflations of an embolectomy catheter in the descending aorta or inferior vena cava. S‑transform time-frequency representations were calculated for multiunit phrenic nerve activity and some spike trains to identify changes in rhythmic activity during perturbations. Altered firing rates in response to either or both conditions were detected for 474 of 704 tested cells. Spike trains of 17,805 neuron pairs were evaluated for short-time scale correlational signatures indicative of functional connectivity with standard cross-correlation analysis, supplemented with gravitational clustering; approximately 70% of tested (498 of 704) and responding neurons (333 of 474) were involved in a functional correlation with at least one other cell. Changes in high frequency oscillations in the spiking of inspiratory neurons and the evocation or resetting of slow quasi-periodic fluctuations in the respiratory motor pattern associated with oscillations of arterial pressure were observed. The results support a linked-loop pontomedullary network architecture for multispectral tuning of inspiration.

Hypoxia evokes a sequence of raphe-pontomedullary network operations for inspiratory drive amplification and gasping

“…To evaluate the short-term consequences of improved gas exchange on the respiratory motor pattern, air was reintroduced into the ventilator and blood pressure was supported to maintain adequate perfusion pressure to the brain and other organ systems. We did not dissociate the extent to which a reduction in blood pressure per se contributed to altered network activity and associated changes in blood pressure, either through reduced brain stem perfusion or altered baroreceptor modulation of the respiratory network (42, 50, 103, 104).…”

“…Data acquisition and analysis. Descriptions of most of the other methods used have been recently published (46,50). Signals from a phrenic nerve were monitored.…”

“…Seven of the eight neuron pairs included an expiratory VRC cell and a target inspiratory VRC cell. Although the precise source of primary gasp-drive in the cat is not known (86)(87)(88), evidence for disinhibitory modulation of inspiratory drive by changes in blood pressure has been reported (50).…”

“…The chain of VRC inspiratory neurons that generates inspiratory drive is continuously tuned by recurrent excitation and by feed-forward and recurrent inhibitory circuits that actively constrain inspiratory drive (43,(45)(46)(47)(48)(49)(50). 5-HT released by the medullary raphe nuclei has been proposed to have a disinhibitory influence on respiratory drive (51,52).…”

“…Thus, our first objective was to test the hypothesis that hypoxia-evoked gasps are amplified through a distributed efference copy mechanism. This mechanism would be expected to generate coordinated gasp-synchronous discharges in other circuits of the raphe-pontomedullary respiratory network simultaneously.The chain of VRC inspiratory neurons that generates inspiratory drive is continuously tuned by recurrent excitation and by feed-forward and recurrent inhibitory circuits that actively constrain inspiratory drive (43,(45)(46)(47)(48)(49)(50). 5-HT released by the medullary raphe nuclei has been proposed to have a disinhibitory influence on respiratory drive (51, 52).…”