A network model of respiratory rhythmogenesis

1992 ◽  
Vol 263 (4) ◽  
pp. R962-R975 ◽  
Author(s):  
M. D. Ogilvie ◽  
A. Gottschalk ◽  
K. Anders ◽  
D. W. Richter ◽  
A. I. Pack
Keyword(s):  
Reasonable Agreement ◽  
Respiratory Rhythm ◽  
Superior Laryngeal Nerve ◽  
Laryngeal Nerve ◽  
Phase Resetting ◽  
Phase Singularity ◽  
Respiratory Rhythmogenesis ◽  
Respiratory Network ◽  
Three Phase ◽  
Model Predictions

A mathematical model of the three-phase respiratory network proposed by Richter et al. (News Physiol. Sci. 1: 109-112, 1986) is developed and its properties are examined. The model reproduces the experimentally determined trajectories of membrane potential for the five physiologically distinct types of neurons included. Stepwise parameter changes can produce a respiratory rhythm with only two separate electrophysiological phases, result in apnea, or produce more complex patterns of firing. The phase-resetting behavior of the model was obtained with perturbing stimuli and is comparable to experimentally determined phase-resetting data. There is reasonable agreement between model predictions and experimental results. In the model, the properties of the phase singularity make termination of the respiratory rhythm by an appropriately timed perturbation virtually impossible, which is in agreement with experimental observations. The rhythm can be stopped by alterations that simulate the effect of input from the superior laryngeal nerve; the rhythm is locked in the postinspiratory phase. We conclude that our results are consistent with the concept of a network oscillator as the source of the respiratory rhythm.

Resetting of mammalian respiratory rhythm: existence of a phase singularity

1986 ◽  
Vol 250 (4) ◽  
pp. R721-R727 ◽  
Author(s):  
D. Paydarfar ◽  
F. L. Eldridge ◽  
J. P. Kiley
Keyword(s):  
Respiratory Rhythm ◽  
Superior Laryngeal Nerve ◽  
Phase Resetting ◽  
Nerve Activity ◽  
Phase Singularity ◽  
Biological Oscillators ◽  
Adult Cats ◽  
The Times ◽  
Qualitative Characteristics

The purpose of this study was to use topological methods of analysis to determine if a phase singularity exists for the neural respiratory oscillator. We studied resetting behavior of central respiratory rhythm, measured as phrenic nerve activity, by using brief stimulations of the superior laryngeal nerve in anesthetized paralyzed adult cats. The strength and timing of stimuli were varied, and the times of onset of subsequent breaths were measured. Two distinct types of phase resetting were identified: type 1 resetting for weak stimuli and type 0 resetting for strong stimuli. With stimuli of intermediate strength, we obtained a series of phase-resetting curves that defined a helicoid-resetting surface having a phase singularity near the transition between late expiration and early inspiration. In this domain resumption of breathing occurred at highly variable resetting times. The mammalian respiratory oscillator thus has qualitative characteristics of response to brief stimuli that are similar to those of other biological oscillators.

scholarly journals Maturation of the Mammalian Respiratory System

1999 ◽  
Vol 79 (2) ◽  
pp. 325-360 ◽  
Author(s):  
Gérard Hilaire ◽  
Bernard Duron
Keyword(s):  
Respiratory Activity ◽  
Respiratory Rhythm ◽  
Ventrolateral Medulla ◽  
Pacemaker Neurons ◽  
Inhibitory Processes ◽  
Respiratory Rhythmogenesis ◽  
Respiratory Network ◽  
Network Functions

In this review, the maturational changes occurring in the mammalian respiratory network from fetal to adult ages are analyzed. Most of the data presented were obtained on rodents using in vitro approaches. In gestational day 18 (E18) fetuses, this network functions but is not yet able to sustain a stable respiratory activity, and most of the neonatal modulatory processes are not yet efficient. Respiratory motoneurons undergo relatively little cell death, and even if not yet fully mature at E18, they are capable of firing sustained bursts of potentials. Endogenous serotonin exerts a potent facilitation on the network and appears to be necessary for the respiratory rhythm to be expressed. In E20 fetuses and neonates, the respiratory activity has become quite stable. Inhibitory processes are not yet necessary for respiratory rhythmogenesis, and the rostral ventrolateral medulla (RVLM) contains inspiratory bursting pacemaker neurons that seem to constitute the kernel of the network. The activity of the network depends on CO2 and pH levels, via cholinergic relays, as well as being modulated at both the RVLM and motoneuronal levels by endogenous serotonin, substance P, and catecholamine mechanisms. In adults, the inhibitory processes become more important, but the RVLM is still a crucial area. The neonatal modulatory processes are likely to continue during adulthood, but they are difficult to investigate in vivo. In conclusion, 1) serotonin, which greatly facilitates the activity of the respiratory network at all developmental ages, may at least partly define its maturation; 2) the RVLM bursting pacemaker neurons may be the kernel of the network from E20 to adulthood, but their existence and their role in vivo need to be further confirmed in both neonatal and adult mammals.

scholarly journals Mechanisms Underlying Adaptation of Respiratory Network Activity to Modulatory Stimuli in the Mouse Embryo

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Marc Chevalier ◽  
Rafaël De Sa ◽  
Laura Cardoit ◽  
Muriel Thoby-Brisson
Keyword(s):  
Ph Regulation ◽  
Respiratory Rhythm ◽  
Network Activity ◽  
Pacemaker Neurons ◽  
Functional Flexibility ◽  
Respiratory Rhythmogenesis ◽  
Brainstem Slice ◽  
Respiratory Network ◽  
The Impact

Breathing is a rhythmic behavior that requires organized contractions of respiratory effector muscles. This behavior must adapt to constantly changing conditions in order to ensure homeostasis, proper body oxygenation, and CO2/pH regulation. Respiratory rhythmogenesis is controlled by neural networks located in the brainstem. One area considered to be essential for generating the inspiratory phase of the respiratory rhythm is the preBötzinger complex (preBötC). Rhythmogenesis emerges from this network through the interplay between the activation of intrinsic cellular properties (pacemaker properties) and intercellular synaptic connections. Respiratory activity continuously changes under the impact of numerous modulatory substances depending on organismal needs and environmental conditions. The preBötC network has been shown to become active during the last third of gestation. But only little is known regarding the modulation of inspiratory rhythmicity at embryonic stages and even less on a possible role of pacemaker neurons in this functional flexibility during the prenatal period. By combining electrophysiology and calcium imaging performed on embryonic brainstem slice preparations, we provide evidence showing that embryonic inspiratory pacemaker neurons are already intrinsically sensitive to neuromodulation and external conditions (i.e., temperature) affecting respiratory network activity, suggesting a potential role of pacemaker neurons in mediating rhythm adaptation to modulatory stimuli in the embryo.

scholarly journals Spatial and Functional Architecture of the Mammalian Brain Stem Respiratory Network: A Hierarchy of Three Oscillatory Mechanisms

2007 ◽  
Vol 98 (6) ◽  
pp. 3370-3387 ◽  
Author(s):  
J. C. Smith ◽  
A. P. L. Abdala ◽  
H. Koizumi ◽  
I. A. Rybak ◽  
J. F. R. Paton
Keyword(s):  
Brain Stem ◽  
Sodium Current ◽  
Respiratory Rhythm ◽  
Central Pattern Generators ◽  
Respiratory Neurons ◽  
Mammalian Brain ◽  
Two Phase ◽  
Respiratory Network ◽  
Three Phase ◽  
The One

Mammalian central pattern generators (CPGs) producing rhythmic movements exhibit extremely robust and flexible behavior. Network architectures that enable these features are not well understood. Here we studied organization of the brain stem respiratory CPG. By sequential rostral to caudal transections through the pontine-medullary respiratory network within an in situ perfused rat brain stem–spinal cord preparation, we showed that network dynamics reorganized and new rhythmogenic mechanisms emerged. The normal three-phase respiratory rhythm transformed to a two-phase and then to a one-phase rhythm as the network was reduced. Expression of the three-phase rhythm required the presence of the pons, generation of the two-phase rhythm depended on the integrity of Bötzinger and pre-Bötzinger complexes and interactions between them, and the one-phase rhythm was generated within the pre-Bötzinger complex. Transformation from the three-phase to a two-phase pattern also occurred in intact preparations when chloride-mediated synaptic inhibition was reduced. In contrast to the three-phase and two-phase rhythms, the one-phase rhythm was abolished by blockade of persistent sodium current ( INaP). A model of the respiratory network was developed to reproduce and explain these observations. The model incorporated interacting populations of respiratory neurons within spatially organized brain stem compartments. Our simulations reproduced the respiratory patterns recorded from intact and sequentially reduced preparations. Our results suggest that the three-phase and two-phase rhythms involve inhibitory network interactions, whereas the one-phase rhythm depends on INaP. We conclude that the respiratory network has rhythmogenic capabilities at multiple levels of network organization, allowing expression of motor patterns specific for various physiological and pathophysiological respiratory behaviors.

Genesis and Control of the Respiratory Rhythm in Adult Mammals

Physiology ◽  
2003 ◽  
Vol 18 (1) ◽  
pp. 23-28 ◽  
Author(s):  
Gérard Hilaire ◽  
Rosario Pásaro
Keyword(s):  
Respiratory Rhythm ◽  
Neural Mechanisms ◽  
Pacemaker Neurons ◽  
Respiratory Rhythmogenesis ◽  
Respiratory Network ◽  
And Control ◽  
Vitro Data ◽  
In Vitro Data

The neural mechanisms responsible for respiratory rhythmogenesis in mammals were studied first in vivo in adults and subsequently in vitro in neonates. In vitro data have suggested that the pacemaker neurons are the kernel of the respiratory network. These data are reviewed, and their relevance to adults is discussed.

scholarly journals The Dynamic Basis of Respiratory Rhythm Generation: One Breath at a Time

2018 ◽  
Vol 41 (1) ◽  
pp. 475-499 ◽  
Author(s):  
Jan-Marino Ramirez ◽  
Nathan A. Baertsch
Keyword(s):  
Coupled Oscillators ◽  
Respiratory Rhythm ◽  
Control Of Breathing ◽  
Lessons Learned ◽  
Rhythm Generation ◽  
Glutamatergic Transmission ◽  
Neuronal Control ◽  
Respiratory Network ◽  
Three Phase ◽  
The Brain

Rhythmicity is a universal timing mechanism in the brain, and the rhythmogenic mechanisms are generally dynamic. This is illustrated for the neuronal control of breathing, a behavior that occurs as a one-, two-, or three-phase rhythm. Each breath is assembled stochastically, and increasing evidence suggests that each phase can be generated independently by a dedicated excitatory microcircuit. Within each microcircuit, rhythmicity emerges through three entangled mechanisms: ( a) glutamatergic transmission, which is amplified by ( b) intrinsic bursting and opposed by ( c) concurrent inhibition. This rhythmogenic triangle is dynamically tuned by neuromodulators and other network interactions. The ability of coupled oscillators to reconfigure and recombine may allow breathing to remain robust yet plastic enough to conform to nonventilatory behaviors such as vocalization, swallowing, and coughing. Lessons learned from the respiratory network may translate to other highly dynamic and integrated rhythmic systems, if approached one breath at a time.

scholarly journals Oscillation patterns are enhanced and firing threshold is lowered in medullary respiratory neuron discharges by threshold doses of a μ-opioid receptor agonist

2017 ◽  
Vol 312 (5) ◽  
pp. R727-R738 ◽  
Author(s):  
Peter M. Lalley ◽  
Steve W. Mifflin
Keyword(s):  
Spike Train ◽  
Brain Stem ◽  
Opioid Receptor ◽  
Respiratory Rhythm ◽  
Opioid Receptor Agonist ◽  
Respiratory Network ◽  
Three Phase ◽  
Μ Opioid Receptor ◽  
Effective Doses ◽  
The Brain

μ-Opioid receptors are distributed widely in the brain stem respiratory network, and opioids with selectivity for μ-type receptors slow in vivo respiratory rhythm in lowest effective doses. Several studies have reported μ-opioid receptor effects on the three-phase rhythm of respiratory neurons, but there are until now no reports of opioid effects on oscillatory activity within respiratory discharges. In this study, effects of the μ-opioid receptor agonist fentanyl on spike train discharge properties of several different types of rhythm-modulating medullary respiratory neuron discharges were analyzed. Doses of fentanyl that were just sufficient for prolongation of discharges and slowing of the three-phase respiratory rhythm also produced pronounced enhancement of spike train properties. Oscillation and burst patterns detected by autocorrelation measurements were greatly enhanced, and interspike intervals were prolonged. Spike train properties under control conditions and after fentanyl were uniform within each experiment, but varied considerably between experiments, which might be related to variability in acid-base balance in the brain stem extracellular fluid. Discharge threshold was shifted to more negative levels of membrane potential. The effects on threshold are postulated to result from opioid-mediated disinhibition and postsynaptic enhancement of N-methyl-d- aspartate receptor current. Lowering of firing threshold, enhancement of spike train oscillations and bursts and prolongation of discharges by lowest effective doses of fentanyl could represent compensatory adjustments in the brain stem respiratory network to override opioid blunting of CO2/pH chemosensitivity.

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