Abstract

Central chemoreceptors are widespread within the brainstem. This conclusion is based on in vitro evidence of neurons from many locations that are responsive to pH changes and on in vivo evidence of respiratory responses to focal acidification at these same locations. Why are there so many chemoreceptor sites? As one possibility we hypothesize that function at different sites varies with arousal state. In unanesthetized rats, we produce focal acidification at single sites with microdialysis (probe tip = 1 mm×240 μm diameter) using artificial cerebrospinal fluid equilibrated with 25% CO2. Tissue acidosis, measured at the region of the retrotrapezoid nucleus (RTN) in unanesthetized rats, is approximately equivalent to that observed with end-tidal PCO2 = 7–8 mmHg above the eupneic value. Focal acidification of the retrotrapezoid nucleus (RTN) increased ventilation by 24% only in wakefulness via an increase in tidal volume [1]. In the medullary raphe, the excitatory effect of such focal acidification was observed only in sleep (defined by EEG and EMG criteria); ventilation and frequency increased by 15–20% in NREM sleep and frequency by 15% in REM sleep. There was no effect in wakefulness [2]. In our most recent study, focal acidification of nucleus tractus solitarius (NTS) increased ventilation by up to 20% in both wakefulness and NREM sleep due to an effect on both tidal volume and frequency. The increase in ventilation is greater with focal acidification in the caudal part of NTS at the level of the area postrema. Acidification of more rostral parts of the NTS produced variable results. The medullary raphe contributes to chemoreception in sleep, the RTN in wakefulness, and the cNTS in both sleep and wakefulness. Central chemoreceptors at these three different locations do appear to vary in effectiveness with arousal state. The response at each site is only a fraction of the response attributable to all sites being stimulated at the same intensity. Hypocapnia resulting from single site stimulation can lower the contribution of other sites minimizing the apparent effectiveness of single site stimulation.

Highlights

  • To be effective, inspiratory muscles on the left and right sides must contract together

  • We have found that a prominent gap in the column of ventral respiratory group (VRG) The nucleus tractus solitarii (NTS) relays information from primary related parvalbumin cells [2] likely corresponds to the pBc since visceral receptors to the central nervous system and is critically parvalbumin cells are rare in this zone and never co-localize with involved in the reflex control of autonomic functions

  • The specific protein(s) necessary for longterm facilitation (LTF) is unknown, we recently found that episodic hypoxia and LTF are associated with elevations in ventral spinal concentrations of brain derived neurotrophic factor (BDNF)

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Summary

Introduction

Inspiratory muscles on the left and right sides must contract together. The left and right halves of the diaphragm are synchronised because a bilateral population of medullary premotor neurones [1] simultaneously excites left and right phrenic motoneurones. Transection studies demonstrate that each side of the brainstem is capable of generating respiratory rhythm independently [2], so that left and right medullary inspiratory neurones must themselves be synchronised. The interconnections and common excitation that accomplish such synchronisation are unknown in rats. The respiratory rhythm of hypoglossal (XII) nerve discharge in transverse medullary slice preparations from neonatal rats is thought to originate in the region of the ventral respiratory group (VRG); generated there by a combination of “pacemaker” neurones [1] and their interactions with other respiratory neurones. Our goal was to discover interconnections between left and right VRG neurones as well as their connections to XII motoneurones

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