Bötzinger Expiratory-Augmenting Neurons and the Parafacial Respiratory Group

Abstract

In neonatal rat brains in vitro, the rostral ventral respiratory column (rVRC) contains neurons that burst just before the phrenic nerve discharge (PND) and rebound after inspiration (pre-I neurons). These neurons, called parafacial respiratory group (pfRG), have been interpreted as a master inspiratory oscillator, an expiratory rhythm generator or simply as neonatal precursors of retrotrapezoid (RTN) chemoreceptor neurons. pfRG neurons have not been identified in adults, and their phenotype is unknown. Here, we confirm that the rVRC normally lacks pre-I neurons in adult anesthetized rats. However, we show that, during hypercapnic hypoxia, a population of rVRC expiratory-augmenting (E-AUG) neurons consistently develops a pre-I discharge. These cells reside in the Bötzinger region of the rVRC, they express glycine-transporter-2, and their axons arborize throughout the VRC. Hypoxia triggers an identical pre-I pattern in retroambigual expiratory bulbospinal neurons, but this pattern is not elicited in Bötzinger expiratory-decrementing neurons, Bötzinger inspiratory neurons, RTN neurons, and blood pressure-regulating neurons. In conclusion, under hypoxia in vivo, abdominal expiratory premotor neurons of adult rats develop a pre-I pattern reminiscent of that observed in neonate brainstems in vitro. In the rVRC of adult rats, pre-I cells include selected rhythmogenic neurons (glycinergic Bötzinger neurons) but not RTN chemoreceptors. We suggest that the pfRG may not be an independent rhythm generator but a heterogeneous collection of E-AUG neurons (glycinergic Bötzinger neurons, possibly facial motor and premotor neurons), the discharge of which becomes preinspiratory under specific experimental conditions resulting from, in part, a prolonged and intensified activity of postinspiratory neurons.

Sympathoexcitation during chemoreflex active expiration is mediated byl-glutamate in the RVLM/Bötzinger complex of rats

“…However, microinjection of KYN into BötC did not abolish the AbN response to chemoreflex activation. To explain why the AbN response to chemoreflex activation was not abolished after bilateral microinjections of KYN into the RVLM/BötC, we must take into account the findings by Fortuna et al (2008) showing that some RTN neurons send projections to the retroambiguus region, the site of premotor bulbospinal expiratory neurons. We observed that the average increase in the magnitude of tSN in response to chemoreflex activation was not affected by bilateral microinjections of KYN into the RVLM/pre-BötC.…”

CO2-Sensitive Preinspiratory Neurons of the Parafacial Respiratory Group Express Phox2b in the Neonatal Rat

“…Consequently, they might be Phox2b-ir cells. A recent study (Fortuna et al, 2008) reported that a population of rostral ventral respiratory neurons (i.e., glycinergic expiratory augmenting neurons) develops a preinspiratory discharge during hypercapnic hypoxia in adult rat in vivo preparations. Despite differences between experimental conditions, these results also support existence of heterogeneous subpopulations of Pre-I neurons in the rostral medulla around the caudal end of the facial nucleus.…”

Pontine respiratory activity involved in inspiratory/expiratory phase transition

“…Motor activity during late (active) expiration emerges during forced breathing and involves active contraction of abdominal and thoracic expiratory muscle groups. The active or late phase of expiration is always present centrally, but in terms of the motor act of exhalation, it may be only activated during high metabolic demands (Fortuna et al 2008) or after experimental challenges involving intermittent hypoxia (Zoccal et al 2008). However, active expiration under physiological conditions is always preceded by post-I and thus, the alternating phases of inspiration and expiration are largely governed by central oscillations between inspiratory and post-I neurons.…”