Reconfiguration of the neural network controlling multiple breathing patterns: eupnea, sighs and gasps

Lieske, Steven P.; Thoby‐Brisson, Muriel; Telgkamp, Petra; Ramirez, Jan‐Marino

doi:10.1038/75776

Cited by 422 publications

(554 citation statements)

References 48 publications

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“…These findings may indicate that the expiratory rhythm generator is dominant over the gasping mechanism, that the hypoxemia was not sufficient to induce gasping, and/or that the gasping center was also eliminated. The latter alternative is consistent with the postulate of Lieske et al (11) that the pre-BötzC is involved in the generation of gasps among other respiratory patterns.…”

Section: Discussionsupporting

confidence: 80%

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

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.-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...

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Section: Discussionsupporting

confidence: 80%

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

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“…Isolation of the PBC in transverse slices in vitro preserves rhythmic activity (Smith et al, 1991), which is characterized by different activity patterns. Quantitative measurements of the frequency, amplitude, and shape of this rhythmic activity led to the discrimination of three very distinct activity patterns that are generated under normoxic and hypoxic conditions (Lieske et al, 2000). In this study, we present data indicating that endogenously released 5-HT acting on the 5-HT 2A receptor is required for the operation of the respiratory network isolated in transverse slices of neonatal mice.…”

Section: Abstract: Respiratory Rhythm; Endogenous Serotonin; Pre-bö mentioning

confidence: 57%

“…As shown in Figure 1 B, DOI increased the frequency of two types of respiratory bursts: small-amplitude bursts that represent "fictive eupneic activity" and large-amplitude bursts that represent "fictive sigh activity" as defined by Lieske et al (2000). In the present study, we evaluated only the serotonergic effect on fictive eupneic activity as defined by Lieske et al (2000) and refer to this activity as "fictive respiratory activity" or "respiratory activity" (small-burst) throughout this study. Frequency of fictive respiratory activity significantly increased to 143 Ϯ 14.2% of control during the application of DOI (Fig.…”

Section: Effects Of Pharmacological Activation and Blockade Of 5-ht 2mentioning

confidence: 99%

Endogenous Activation of Serotonin-2A Receptors Is Required for Respiratory Rhythm GenerationIn Vitro

2002

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Endogenous amines and peptides continuously modulate the activity of neuronal networks and are required even for their normal operation. The respiratory rhythm generator, localized in the pre-Bö tzinger complex, is not an exception. This network is modulated by various neurotransmitters, including serotonin (5-HT). In this study, we isolated the respiratory network in brainstem slices and demonstrate that the endogenous activation of 5-HT 2A is required for the generation of the respiratory rhythm in vitro. At the network level, activation of 5-HT 2A receptors with 4-iodo-2,5-dimethoxyamphetamine or the 5-HT uptake blocker alaproclate increased the frequency of respiratory activity. Blockade of endogenously activated 5-HT 2A receptors with three different antagonists decreased the frequency, amplitude, and regularity of respiratory population activity, an effect that was blocked by protein kinase C (PKC) activators. At the cellular level, blockade of 5-HT 2A receptors reduced the action potential discharge in all examined respiratory neurons, which was associated with a reduction in the fast and the persistent sodium current. Continuous application of 5-HT 2A -receptor antagonists differentially affected pacemaker neurons. Pacemaker activity was eliminated in cadmiuminsensitive pacemaker neurons. In cadmium-sensitive pacemaker neurons, the frequency of pacemaker activity was unaffected and the amplitude of pacemaker bursts was enhanced. It is assumed that cadmium-insensitive pacemakers rely on the persistent sodium current, whereas cadmium-sensitive pacemakers depend on the activation of calcium currents. We conclude that endogenously activated 5-HT 2A receptors are required for maintaining fictive respiratory activity in the brainstem slice by modulating sodium conductances via a PKC pathway.

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“…This result implies that forebrain control of brain stem respiratory CPGs is rapid and precise during behavior, similar to the peripheral control of respiration . One possibility is that there are different CPGs underlying these distinct sniffing modes, which may constitute discrete networks that are either within the same region or in different brain regions (Feldman and Del Negro 2006;Janczewski and Feldman 2006;Onimaru and Homma 2003) Alternatively, it may be that the same pre-Bötzinger complex that is responsible for normal breathing can be rapidly reconfigured to generate multiple motor patterns (Arata et al 2000;Lieske et al 2000), perhaps by neuromodulation (Marder and Calabrese 1996). Either way, afferent feedback from higher brain areas to the respiratory center must be able to transform network output quite rapidly, within a single respiration cycle, and do so in an anticipatory manner.…”

Section: Rapid Switching Between Sniffing Modesmentioning

confidence: 99%

Rapid and Precise Control of Sniffing During Olfactory Discrimination in Rats

Kepecs

Uchida

Mainen

2007

Journal of Neurophysiology

187

199

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Kepecs A, Uchida N, Mainen ZF. Rapid and precise control of sniffing during olfactory discrimination in rats. J Neurophysiol 98: 205-213, 2007. First published April 25, 2007 doi:10.1152/jn.00071.2007. Olfactory perception relies on an active sampling process, sniffing, to rapidly deliver odorants from the environment to the olfactory receptors. The respiration cycle strongly patterns the flow of information into the olfactory systems, but the behavioral significance of particular sniffing patterns is not well understood. Here, we monitored the frequency and timing of nasal respiration in rats performing an odor-mixture-discrimination task that allowed us to test subjects near psychophysical limits and to quantify the precise timing of their behavior. We found that respiration frequencies varied widely from 2 to 12 Hz, but odor discrimination was dependent on 6-to 9-Hz sniffing: rats almost always entered and maintained this frequency band during odor sampling and their accuracy on difficult discrimination dropped when they did not. Moreover, the switch from baseline respiration to sniffing occurred not in response to odor delivery but in anticipation of odor sampling and was executed rapidly, almost always within a single cycle. Interestingly, rats also switched from respiration to rapid sniffing in anticipation of reward delivery, but in a distinct frequency band, 9 -12 Hz. These results demonstrate the speed and precision of control over respiration and its significance for olfactory behavioral performance.

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Reconfiguration of the neural network controlling multiple breathing patterns: eupnea, sighs and gasps

Cited by 422 publications

References 48 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

Endogenous Activation of Serotonin-2A Receptors Is Required for Respiratory Rhythm GenerationIn Vitro

Rapid and Precise Control of Sniffing During Olfactory Discrimination in Rats

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