Effect of hypoxia on the activity of respiratory and non-respiratory modulated retrotrapezoid neurons of the cat

Bodineau, Laurence; Frugière, Alain; Marlot, D.; Wallois, Fabrice

doi:10.1016/s1566-0702(00)00237-x

Cited by 19 publications

(19 citation statements)

References 26 publications

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“…Since these responses were observed only in rats with intact carotid chemoreceptors, they depended entirely on afferent inputs from these organs. These results are congruent with prior J Physiol 572.2 experimentation in rats and cats (Bodineau et al 2000b;Mulkey et al 2004). Carotid chemoreceptor afferents primarily innervate commNTS (Blessing et al 1999).…”

Section: Rtn Neurons Receive Oligo-synaptic Excitatory Inputs From Casupporting

confidence: 89%

Peripheral chemoreceptor inputs to retrotrapezoid nucleus (RTN) CO₂‐sensitive neurons in rats

Takakura

Moreira

Colombari

et al. 2006

The Journal of Physiology

292

329

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The rat retrotrapezoid nucleus (RTN) contains pH-sensitive neurons that are putative central chemoreceptors. Here, we examined whether these neurons respond to peripheral chemoreceptor stimulation and whether the input is direct from the solitary tract nucleus (NTS) or indirect via the respiratory network. A dense neuronal projection from commissural NTS (commNTS) to RTN was revealed using the anterograde tracer biotinylated dextran amine (BDA). Within RTN, 51% of BDA-labelled axonal varicosities contained detectable levels of vesicular glutamate transporter-2 (VGLUT2) but only 5% contained glutamic acid decarboxylase-67 (GAD67). Awake rats were exposed to hypoxia (n = 6) or normoxia (n = 5) 1 week after injection of the retrograde tracer cholera toxin B (CTB) into RTN. Hypoxia-activated neurons were identified by the presence of Fos-immunoreactive nuclei. CommNTS neurons immunoreactive for both Fos and CTB were found only in hypoxia-treated rats. VGLUT2 mRNA was detected in 92 ± 13% of these neurons whereas only 12 ± 9% contained GAD67 mRNA. In urethane-chloralose-anaesthetized rats, bilateral inhibition of the RTN with muscimol eliminated the phrenic nerve discharge (PND) at rest, during hyperoxic hypercapnia (10% CO 2 ), and during peripheral chemoreceptor stimulation (hypoxia and/or I.V. sodium cyanide, NaCN). RTN CO 2 -activated neurons were recorded extracellularly in anaesthetized intact or vagotomized rats. These neurons were strongly activated by hypoxia (10-15% O 2 ; 30 s) or by NaCN. Hypoxia and NaCN were ineffective in rats with carotid chemoreceptor denervation. Bilateral injection of muscimol into the ventral respiratory column 1.5 mm caudal to RTN eliminated PND and the respiratory modulation of RTN neurons. Muscimol did not change the threshold and sensitivity of RTN neurons to hyperoxic hypercapnia nor their activation by peripheral chemoreceptor stimulation. In conclusion, RTN neurons respond to brain P CO 2 presumably via their intrinsic chemosensitivity and to carotid chemoreceptor activation via a direct glutamatergic pathway from commNTS that bypasses the respiratory network. RTN neurons probably contribute a portion of the chemical drive to breathe. The chemical drive to breathe relies on central chemoreceptors that detect brain extracellular fluid P CO 2 via pH, and on carotid body chemoreceptors that respond to arterial P CO 2 in a P O 2 -and glucose-dependent manner (Scheid et al.

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Section: Rtn Neurons Receive Oligo-synaptic Excitatory Inputs From Casupporting

confidence: 89%

Peripheral chemoreceptor inputs to retrotrapezoid nucleus (RTN) CO₂‐sensitive neurons in rats

Takakura

Moreira

Colombari

et al. 2006

The Journal of Physiology

292

329

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“…In essence, we hypothesize that the CPG input to the chemosensitive neurons of RTN/pfRG is a simple feedback. This feedback originates from phasically active respiratory neurons and therefore produces the respiratory modulation of RTN/pfRG previously observed under various experimental conditions (Connelly et al, 1990;Nattie et al, 1993;Onimaru et al, 1995;Bodineau et al, 2000;Takeda et al, 2001;Janczewski et al, 2002;Onimaru and Homma, 2003).…”

Section: Introductionmentioning

confidence: 86%

“…Their discharges are more strongly phase locked to PND and typically synchronized with inspiration or expiration rather than phase spanning or biphasic (Connelly et al, 1990;Nattie et al, 1993;Bodineau et al, 2000). However, respiratory patterns can be species or anesthetic related, and, although the chemosensitivity of cat's RTN neurons is untested, a functional homology between rat's and cat's RTN neurons remains plausible (for further discussion of the comparative anatomy of RTN, see Weston et al, 2004).…”

Section: The Respiratory Modulation Of Rtn Neurons Is Attributable Tomentioning

confidence: 99%

Regulation of Ventral Surface Chemoreceptors by the Central Respiratory Pattern Generator

Guyenet

Mulkey²,

Stornetta³

et al. 2005

J. Neurosci.

165

272

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The rat retrotrapezoid nucleus (RTN) contains neurons described as central chemoreceptors in the adult and respiratory rhythmgenerating pacemakers in neonates [parafacial respiratory group (pfRG)]. Here we test the hypothesis that both RTN and pfRG neurons are intrinsically chemosensitive and tonically firing neurons whose respiratory rhythmicity is caused by a synaptic feedback from the central respiratory pattern generator (CPG). In halothane-anesthetized adults, RTN neurons were silent below 4.5% end-expiratory (e-exp) CO 2 . Their activity increased linearly (3.2 Hz/1% CO 2 ) up to 6.5% (CPG threshold) and then more slowly to peak ϳ10 Hz at 10% CO 2 . Respiratory modulation of RTN neurons was absent below CPG threshold, gradually stronger beyond, and, like pfRG neurons, typically (42%) characterized by twin periods of reduced activity near phrenic inspiration. After CPG inactivation with kynurenate (KYN), RTN neurons discharged linearly as a function of e-exp CO 2 (slope, ϩ1.7 Hz/1% CO 2 ) and arterial pH (threshold, 7.48; slope, 39 Hz/pH unit). In coronal brain slices (postnatal days 7-12), RTN chemosensitive neurons were silent at pH 7.55. Their activity increased linearly with acidification up to pH 7.2 (17 Hz/pH unit at 35°C) and was always tonic.In conclusion, consistent with their postulated central chemoreceptor role, RTN/pfRG neurons encode pH linearly and discharge tonically when disconnected from the rest of the respiratory centers in vivo (KYN treatment) and in vitro. In vivo, RTN neurons receive respiratory synchronous inhibitory inputs that may serve as feedback and impart these neurons with their characteristic respiratory modulation.

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“…In vivo, hypoxia elicits a biphasic respiratory response that consists of an initial increase, followed by a reduction of the respiratory output (25,26). The initial increase is essentially triggered by excitatory inputs from the peripheral chemoreceptors (25) with the participation of hypothalamic areas (27), whereas the hypoxic respiratory depression (HRD) seems to arise from a central origin (25) in which ponto-medullary areas seem to play a key role (28,29). The brainstem-spinal cord preparation has been shown to respond to hypoxia with a reversible decrease in Rf and was used successfully for breaking down the ponto-medullary mechanisms underlying the HRD (18, 20, 21, 30 -32).…”

Section: Perinatal Respiration and Caffeinementioning

confidence: 99%

“…A high level of Fos expression in the RTN brings new elements in favor of a key role played by this area in the HRD. RTN neurons have been primarily reported to be involved in the central pathway activated by hypoxia (17,29,41,42), and recently, they have been proposed to trigger or relay a central depressive influence of hypoxia on the respiratory network (21). Because the RTN is the only structure that presented a hypoxia-evoked elevation of Fos expression, one may suppose that either it contains O 2 -sensing neurons or it is submitted to the removal of inhibitory influences exerted by other areas.…”

Section: Effect Of Hypoxia On the Central Respiratory Output And Relamentioning

confidence: 99%

Consequences of In Utero Caffeine Exposure on Respiratory Output in Normoxic and Hypoxic Conditions and Related Changes of Fos Expression: A Study on Brainstem-Spinal Cord Preparations Isolated From Newborn Rats

et al. 2003

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Several aspects of the central regulation of respiratory control have been investigated on brainstem-spinal cord preparations isolated from newborn rats whose dam was given 0.02% caffeine in water as drinking fluid during the whole period of pregnancy. Analysis of the central respiratory drive estimated by the recording of C4 ventral root activity was correlated to Fos pontomedullary expression. Under normoxic conditions, preparations obtained from the caffeine-treated group of animals displayed a higher respiratory frequency than observed in the control group (9.2 Ϯ 0.5 versus 7.2 Ϯ 0.6 burst/min). A parallel Fos detection tends to indicate that the changes of the respiratory rhythm may be due to a decrease in neuronal activity of medullary structures such as the ventrolateral subdivision of the solitary tract, the area postrema, and the nucleus raphe obscurus. Under hypoxic conditions, the preparations displayed a typical hypoxic respiratory depression associated with changes in the medullary Fos expression pattern. In addition, the hypoxic respiratory depression is clearly emphasized after in utero exposure to caffeine and coincides with an increased Fos expression in the area postrema and nucleus raphe obscurus, two structures in which it is not increased in the absence of caffeine. Taken together, these results support the idea that in utero caffeine exposure could affect central respiratory control. Caffeine, which belongs to the methylxanthine family, is commonly ingested in various beverages such as coffee, tea, or cola drink (1). It interacts with adenosine neuronal transmitter system as an A 1 and A 2A receptor antagonist (2) and has been shown to alter the adenosinergic transmission upon chronic administration (3-5).In rats, a positive correlation has been established between exposure to caffeine during gestation and a reduction of the fetal cerebral weight (6). Such an observation could lead to propose that caffeine modifies maturational neuronal processes. Moreover, various studies reported that a sustained maternal caffeine intake induces harmful physiologic effects on human newborns (for review, see 7). Among these effects, respiratory perturbations have been described (8 -10). Nevertheless, the existence of a relation between exposure to caffeine during pregnancy and the occurrence of respiratory perturbations in

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Effect of hypoxia on the activity of respiratory and non-respiratory modulated retrotrapezoid neurons of the cat

Cited by 19 publications

References 26 publications

Peripheral chemoreceptor inputs to retrotrapezoid nucleus (RTN) CO₂‐sensitive neurons in rats

Peripheral chemoreceptor inputs to retrotrapezoid nucleus (RTN) CO₂‐sensitive neurons in rats

Regulation of Ventral Surface Chemoreceptors by the Central Respiratory Pattern Generator

Consequences of In Utero Caffeine Exposure on Respiratory Output in Normoxic and Hypoxic Conditions and Related Changes of Fos Expression: A Study on Brainstem-Spinal Cord Preparations Isolated From Newborn Rats

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Effect of hypoxia on the activity of respiratory and non-respiratory modulated retrotrapezoid neurons of the cat

Cited by 19 publications

References 26 publications

Peripheral chemoreceptor inputs to retrotrapezoid nucleus (RTN) CO2‐sensitive neurons in rats

Peripheral chemoreceptor inputs to retrotrapezoid nucleus (RTN) CO2‐sensitive neurons in rats

Regulation of Ventral Surface Chemoreceptors by the Central Respiratory Pattern Generator

Consequences of In Utero Caffeine Exposure on Respiratory Output in Normoxic and Hypoxic Conditions and Related Changes of Fos Expression: A Study on Brainstem-Spinal Cord Preparations Isolated From Newborn Rats

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Peripheral chemoreceptor inputs to retrotrapezoid nucleus (RTN) CO₂‐sensitive neurons in rats

Peripheral chemoreceptor inputs to retrotrapezoid nucleus (RTN) CO₂‐sensitive neurons in rats