Opioid‐resistant respiratory pathway from the preinspiratory neurones to abdominal muscles: <i>in vivo</i> and <i>in vitro</i> study in the newborn rat

Janczewski, Wiktor A.; Onimaru, Hiroshi; Homma, Ikuo; Feldman, Jack L.

doi:10.1113/jphysiol.2002.023408

Cited by 159 publications

(183 citation statements)

References 46 publications

Supporting

Mentioning

163

Contrasting

Unclassified

Order By: Relevance

“…These data provide evidence of a second rhythm generator (expiratory), which is only expressed with depression of the inspiratory rhythm generator. This expiratory rhythm generator is rostral to the pre-BötzC area ventrolateral to the rostral Bötzinger complex and/or in the parafacial region (4,8,14,17). In goats during the tachypneic period following IA injections, rhythmic abdominal muscle activity was clearly present, and it was characteristically 180°o ut of phase with diaphragm activity.…”

Section: Discussionmentioning

confidence: 95%

“…Janczewski et al (8) and Mellen et al (14) have recently demonstrated expression of rhythmic expiratory muscle respiratoryrelated activity following a -opioid-induced depression of pre-BötzC inspiratory neurons. These data provide evidence of a second rhythm generator (expiratory), which is only expressed with depression of the inspiratory rhythm generator.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, in vivo studies in anesthetized or decerebrate cats or rats demonstrate that lesioning of the pre-BötzC results in transient (24) or irreversible (7, 10, 18) elimination of eupneic respiratory activity. Further demonstrating the importance of the pre-BötzC in control of breathing was a study showing that Ͼ80% destruction of neurokinin-1 receptor (NK1R)-expressing neurons in the pre-BötzC resulted in an ataxic breathing pattern and hypoventilation in awake rats (6).Recently, it has been proposed that, within the medulla, there are two respiratory rhythm generators, which are mutually inhibitory and each capable of generating a rhythm under different conditions: one is an inspiratory generator composed of pre-BötzC inspiratory neurons, and the second is an expiratory generator composed of preinspiratory (pre-I) neurons ventrolateral to the rostral Bötzinger complex (4,8,14,17). Supposedly, the pre-BötzC rhythm generator is normally dominant, and it inhibits the rostral pre-I neurons (14), which initiate rhythmic abdominal muscle contraction when preBötzC inspiratory neuronal activity is depressed (4, 8).…”

mentioning

confidence: 99%

“…Supposedly, the pre-BötzC rhythm generator is normally dominant, and it inhibits the rostral pre-I neurons (14), which initiate rhythmic abdominal muscle contraction when preBötzC inspiratory neuronal activity is depressed (4,8).…”

mentioning

confidence: 99%

“…Recently, it has been proposed that, within the medulla, there are two respiratory rhythm generators, which are mutually inhibitory and each capable of generating a rhythm under different conditions: one is an inspiratory generator composed of pre-BötzC inspiratory neurons, and the second is an expiratory generator composed of preinspiratory (pre-I) neurons ventrolateral to the rostral Bötzinger complex (4,8,14,17). Supposedly, the pre-BötzC rhythm generator is normally dominant, and it inhibits the rostral pre-I neurons (14), which initiate rhythmic abdominal muscle contraction when preBötzC inspiratory neuronal activity is depressed (4,8).…”

mentioning

confidence: 99%

See 4 more Smart Citations

Large lesions in the pre-Bötzinger complex area eliminate eupneic respiratory rhythm in awake goats

Wenninger

Pan

Klum

et al. 2004

Journal of Applied Physiology

View full text Add to dashboard Cite

.-In awake goats, 29% bilateral destruction of neurokinin-1 receptorexpressing neurons in the pre-Bötzinger complex (pre-BötzC) area with saporin conjugated to substance P results in transient disruptions of the normal pattern of eupneic respiratory muscle activation (Wenninger JM, Pan LG, Klum L, Leekley T, Bastastic J, Hodges MR, Feroah T, Davis S, and Forster HV. J Appl Physiol 97: 1620 -1628, 2004). Therefore, the purpose of these studies was to determine whether large or total lesioning in the pre-BötzC area of goats would eliminate phasic diaphragm activity and the eupneic breathing pattern. In awake goats that already had 29% bilateral destruction of neurokinin-1 receptor-expressing neurons in the pre-BötzC area, bilateral ibotenic acid (10 l, 50 mM) injection into the pre-BötzC area resulted in a tachypneic hyperpnea that reached a maximum (132 Ϯ 10.1 breaths/min) ϳ30 -90 min after bilateral injection. Thereafter, breathing frequency declined, central apneas resulted in arterial hypoxemia (arterial PO 2 ϳ40 Torr) and hypercapnia (arterial PCO2 ϳ60 Torr), and, 11 Ϯ 3 min after the peak tachypnea, respiratory failure was followed by cardiac arrest in three airway-intact goats. However, after the peak tachypnea in four tracheostomized goats, mechanical ventilation was initiated to maintain arterial blood gases at control levels, during which there was no phasic diaphragm or abdominal muscle activity. When briefly removed from the ventilator (ϳ90 s), these goats became hypoxemic and hypercapnic. During this time, minimal, passive inspiratory flow resulted from phasic abdominal muscle activity. We estimate that 70% of the neurons within the pre-BötzC area were lesioned in these goats. We conclude that, in the awake state, the pre-BötzC is critical for generating a diaphragm, eupneic respiratory rhythm, and that, in the absence of the pre-BötzC, spontaneous breathing reflects the activity of an expiratory rhythm generator. respiratory rhythm generator; terminal apnea; inspiratory and preinspiratory neurons SMITH ET AL. (21) DEMONSTRATED in the in vitro neonatal rat brain stem preparation that elimination of the pre-Bötzinger complex (pre-BötzC) caused cessation of respiratory rhythm. Since then, results from many in vitro studies support the pre-BötzC as the site or "kernel" of respiratory rhythm generation (9,19,20,21). Furthermore, in in vivo studies on anesthetized cats and rats, injection of the glutamate receptor agonist DL-homocysteic acid into the pre-BötzC area increases tonic and/or phasic phrenic nerve output, whereas injections into other proximal or distal nuclei do not increase respiratory rhythm (1,15,22), thus providing a physiological definition of the preBötzC. In addition, in vivo studies in anesthetized or decerebrate cats or rats demonstrate that lesioning of the pre-BötzC results in transient (24) or irreversible (7, 10, 18) elimination of eupneic respiratory activity. Further demonstrating the importance of the pre-BötzC in control of breathing was a study showing that Ͼ80% destruction o...

show abstract

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Large lesions in the pre-Bötzinger complex area eliminate eupneic respiratory rhythm in awake goats

Wenninger

Pan

Klum

et al. 2004

Journal of Applied Physiology

View full text Add to dashboard Cite

show abstract

Afferent and efferent connections of the rat retrotrapezoid nucleus

2006

View full text Add to dashboard Cite

The rat retrotrapezoid nucleus (RTN) contains candidate central chemoreceptors that have extensive dendrites within the marginal layer (ML). This study describes the axonal projections of RTN neurons and their probable synaptic inputs. The ML showed a dense plexus of nerve terminals immunoreactive (ir) for markers of glutamatergic (vesicular glutamate transporters VGLUT1-3), gamma-aminobutyric acid (GABA)-ergic, adrenergic, serotonergic, cholinergic, and peptidergic transmission. The density of VGLUT3-ir terminals tracked the location of RTN chemoreceptors. The efferent and afferent projections of RTN were studied by placing small iontophoretic injections of anterograde (biotinylated dextran amine; BDA) and retrograde (cholera toxin B) tracers where RTN chemoreceptors have been previously recorded. BDA did not label the nearby C1 cells. BDA-ir varicosities were found in the solitary tract nucleus (NTS), all ventral respiratory column (VRC) subdivisions, A5 noradrenergic area, parabrachial complex, and spinal cord. In each target region, a large percentage of the BDA-ir varicosities was VGLUT2-ir (41-83%). Putative afferent input to RTN originated from spinal cord, caudal NTS, area postrema, VRC, dorsolateral pons, raphe nuclei, lateral hypothalamus, central amygdala, and insular cortex. The results suggest that 1) whether or not the ML is specialized for CO(2) sensing, its complex neuropil likely regulates the activity of RTN chemosensitive neurons; 2) the catecholaminergic, cholinergic, and serotonergic innervation of RTN represents a possible substrate for the known state-dependent control of RTN chemoreceptors; 3) VGLUT3-ir terminals are a probable marker of RTN; and 4) the chemosensitive neurons of RTN may provide a chemical drive to multiple respiratory outflows, insofar as RTN innervates the entire VRC.

show abstract

Projections of preBötzinger Complex neurons in adult rats

Tan

Pagliardini

Yang

et al. 2010

J of Comparative Neurology

Self Cite

128

134

View full text Add to dashboard Cite

The preBötzinger Complex (preBötC) contains neural microcircuitry essential for normal respiratory rhythm generation in rodents. A subpopulation of preBötC neurons expresses somatostatin, a neuropeptide with a modulatory action on breathing. Acute silencing of a subpopulation of preBötC neurons transfected by a virus driving protein expression under the somatostatin promoter results in persistent apnea in awake adult rats. Given the profound effect of silencing these neurons, their projections are of interest. We used an adeno-associated virus to overexpress enhanced green fluorescent protein driven by the somatostatin promoter in preBötC neurons to label their axons and terminal fields. These neurons send brainstem projections to: 1) contralateral preBötC; 2) ipsi- and contralateral Bötzinger Complex; 3) ventral respiratory column caudal to preBötC; 4) parafacial respiratory group / retrotrapezoid nucleus; 5) parahypoglossal nucleus/nucleus of the solitary tract; 6) parabrachial/Kölliker-Fuse nuclei; and 7) periaqueductal gray. We did not find major projections to either cerebellum or spinal cord. We conclude that there are widespread projections from preBötC somatostatin-expressing neurons specifically targeted to brainstem regions implicated in control of breathing, and provide a network basis for the profound effects and the essential role of the preBötC in breathing.

show abstract

Opioid‐resistant respiratory pathway from the preinspiratory neurones to abdominal muscles: in vivo and in vitro study in the newborn rat

Abstract: Journal of Physiologytransmitting it to L1 motoneurones, by using the in vitro brainstem-spinal cord preparation.

Cited by 159 publications

References 46 publications

Large lesions in the pre-Bötzinger complex area eliminate eupneic respiratory rhythm in awake goats

Large lesions in the pre-Bötzinger complex area eliminate eupneic respiratory rhythm in awake goats

Afferent and efferent connections of the rat retrotrapezoid nucleus

Projections of preBötzinger Complex neurons in adult rats

Contact Info

Product

Resources

About