scholarly journals Influence of Electric Current and Magnetic Flow on Firing Patterns of Pre-Bötzinger Complex Model

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Wenchao Ji ◽  
Moutian Liu ◽  
Lixia Duan
Keyword(s):  
Electric Current ◽  
Respiratory Rhythm ◽  
Complex Model ◽  
Neuronal Firing ◽  
Essential Factor ◽  
Firing Activity ◽  
Magnetic Flow ◽  
Bötzinger Complex ◽  
Bistable Structure ◽  
Slow Decomposition

The dynamics of neuronal firing activity is vital for understanding the pathological respiratory rhythm. Studies on electrophysiology show that the magnetic flow is an essential factor that modulates the firing activities of neurons. By adding the magnetic flow to Butera’s neuron model, we investigate how the electric current and magnetic flow influence neuronal activities under certain parametric restrictions. Using fast-slow decomposition and bifurcation analysis, we show that the variation of external electric current and magnetic flow leads to the change of the bistable structure of the system and hence results in the switch of neuronal firing pattern from one type to another.

Transition Mechanisms of Bursting in a Two-Cell Network Model of the Pre-Bötzinger Complex

2015 ◽  
Vol 25 (05) ◽  
pp. 1550069 ◽  
Author(s):  
Lixia Duan ◽  
Dandan Yuan ◽  
Xi Chen ◽  
Xiangying Meng
Keyword(s):  
Network Model ◽  
Parameter Space ◽  
Respiratory Rhythm ◽  
Rhythm Generation ◽  
Synaptic Coupling ◽  
Cell Network ◽  
Bötzinger Complex ◽  
Respiratory Rhythm Generation ◽  
Two Parameter ◽  
Slow Decomposition

Persistent sodium and calcium activated nonspecific cationic currents play important roles in the respiratory rhythm generation of the pre-Bötzinger complex. In this paper, we study the bursting patterns and their transition mechanisms in the two-parameter space of a two-cell network model of the pre-Bötzinger complex with synaptic coupling. Using the methods of fast/slow decomposition and two-parameter bifurcation analysis, we divide the two-parameter space into four different regions according to the multiphase oscillations, and reveal the possible transition mechanisms of bursting between these different regions. We also study the dynamics of the system with varying synaptic coupling strength. This work provides insights of how currents and synaptic coupling work on the respiratory rhythm generation.

scholarly journals Dynamics Analysis of Firing Patterns in Pre-Bötzinger Complex Neurons Model

2021 ◽  
Vol 15 ◽  
Author(s):  
Quan Yuan ◽  
Jieqiong Xu ◽  
Huiying Chen
Keyword(s):  
Respiratory Rhythm ◽  
Compartment Model ◽  
Mammalian Brain ◽  
Firing Patterns ◽  
Cation Current ◽  
Stimulus Current ◽  
Bötzinger Complex ◽  
Single Compartment Model ◽  
Respiratory Rhythms ◽  
Slow Decomposition

Pre-Bötzinger complex (PBC) neurons located in mammalian brain are the necessary conditions to produce respiratory rhythm, which has been widely verified experimentally and numerically. At present, one of the two different types of bursting mechanisms found in PBC mainly depends on the calcium-activated of non-specific cation current (ICaN). In order to study the influence of ICaN and stimulus current Iexc in PBC inspiratory neurons, a single compartment model was simplified, and firing patterns of the model was discussed by using stability theory, bifurcation analysis, fast, and slow decomposition technology combined with numerical simulation. Under the stimulation of different somatic applied currents, the firing behavior of neurons are studied and exhibit multiple mix bursting patterns, which is helpful to further understand the mechanism of respiratory rhythms of PBC neurons.

Pre-Bötzinger Complex Functions as a Central Hypoxia Chemosensor for Respiration In Vivo

2000 ◽  
Vol 83 (5) ◽  
pp. 2854-2868 ◽  
Author(s):  
Irene C. Solomon ◽  
Norman H. Edelman ◽  
Judith A. Neubauer
Keyword(s):  
Short Duration ◽  
Phrenic Nerve ◽  
Excitatory Amino Acid ◽  
Respiratory Rhythm ◽  
High Amplitude ◽  
Unique Region ◽  
Homocysteic Acid ◽  
Bötzinger Complex ◽  
Nerve Discharge

Recently, we identified a region located in the pre-Bötzinger complex (pre-BötC; the proposed locus of respiratory rhythm generation) in which activation of ionotropic excitatory amino acid receptors usingdl-homocysteic acid (DLH) elicits a variety of excitatory responses in the phrenic neurogram, ranging from tonic firing to a rapid series of high-amplitude, rapid rate of rise, short-duration inspiratory bursts that are indistinguishable from gasps produced by severe systemic hypoxia. Therefore we hypothesized that this unique region is chemosensitive to hypoxia. To test this hypothesis, we examined the response to unilateral microinjection of sodium cyanide (NaCN) into the pre-BötC in chloralose- or chloralose/urethan-anesthetized vagotomized, paralyzed, mechanically ventilated cats. In all experiments, sites in the pre-BötC were functionally identified using DLH (10 mM, 21 nl) as we have previously described. All sites were histologically confirmed to be in the pre-BötC after completion of the experiment. Unilateral microinjection of NaCN (1 mM, 21 nl) into the pre-BötC produced excitation of phrenic nerve discharge in 49 of the 81 sites examined. This augmentation of inspiratory output exhibited one of the following changes in cycle timing and/or pattern: 1) a series of high-amplitude, short-duration bursts in the phrenic neurogram (a discharge similar to a gasp), 2) a tonic excitation of phrenic neurogram output, 3) augmented bursts in the phrenic neurogram (i.e., eupneic breath ending with a gasplike burst), or 4) an increase in frequency of phrenic bursts accompanied by small increases or decreases in the amplitude of integrated phrenic nerve discharge. Our findings identify a locus in the brain stem in which focal hypoxia augments respiratory output. We propose that the respiratory rhythm generator in the pre-BötC has intrinsic hypoxic chemosensitivity that may play a role in hypoxia-induced gasping.

Models of Respiratory Rhythm Generation in the Pre-Bötzinger Complex. I. Bursting Pacemaker Neurons

1999 ◽  
Vol 82 (1) ◽  
pp. 382-397 ◽  
Author(s):  
Robert J. Butera ◽  
John Rinzel ◽  
Jeffrey C. Smith
Keyword(s):  
Membrane Potential ◽  
Respiratory Rhythm ◽  
Rhythm Generation ◽  
Minimal Models ◽  
Dynamic Features ◽  
Bursting Neurons ◽  
Wide Range ◽  
Bötzinger Complex ◽  
Voltage Dependent ◽  
Respiratory Rhythm Generation

A network of oscillatory bursting neurons with excitatory coupling is hypothesized to define the primary kernel for respiratory rhythm generation in the pre-Bötzinger complex (pre-BötC) in mammals. Two minimal models of these neurons are proposed. In model 1, bursting arises via fast activation and slow inactivation of a persistent Na+ current I NaP-h. In model 2, bursting arises via a fast-activating persistent Na+ current INaP and slow activation of a K+ current IKS. In both models, action potentials are generated via fast Na+ and K+currents. The two models have few differences in parameters to facilitate a rigorous comparison of the two different burst-generating mechanisms. Both models are consistent with many of the dynamic features of electrophysiological recordings from pre-BötC oscillatory bursting neurons in vitro, including voltage-dependent activity modes (silence, bursting, and beating), a voltage-dependent burst frequency that can vary from 0.05 to >1 Hz, and a decaying spike frequency during bursting. These results are robust and persist across a wide range of parameter values for both models. However, the dynamics of model 1 are more consistent with experimental data in that the burst duration decreases as the baseline membrane potential is depolarized and the model has a relatively flat membrane potential trajectory during the interburst interval. We propose several experimental tests to demonstrate the validity of either model and to differentiate between the two mechanisms.

scholarly journals Lethal avian influenza A (H5N1) virus induces ataxic breathing in mice with apoptosis of pre-Botzinger complex neurons expressing neurokinin-1 receptor

2017 ◽  
Vol 313 (5) ◽  
pp. L772-L780 ◽  
Author(s):  
Jianguo Zhuang ◽  
Na Zang ◽  
Chunyan Ye ◽  
Fadi Xu
Keyword(s):  
Respiratory Failure ◽  
Influenza A ◽  
Early Stage ◽  
Respiratory Rhythm ◽  
Body Weight Loss ◽  
Neurokinin 1 Receptor ◽  
Arterial Blood ◽  
Bötzinger Complex ◽  
Neurokinin 1 ◽  
Active Caspase

Lethal influenza A (H5N1) induces respiratory failure in humans. Although it also causes death at 7 days postinfection (dpi) in mice, the development of the respiratory failure and the viral impact on pre-Botzinger complex (PBC) neurons expressing neurokinin 1 receptor (NK1R), which is the respiratory rhythm generator, have not been explored. Body temperature, weight, ventilation, and arterial blood pH and gases were measured at 0, 2, 4, and 6 dpi in control, lethal HK483, and nonlethal HK486 viral-infected mice. Immunoreactivities (IR) of PBC NK1R, H5N1 viral nucleoprotein (NP), and active caspase-3 (CASP3; a marker for apoptosis) were detected at 6 dpi. HK483, but not HK486, mice showed the following abnormalities: 1) gradual body weight loss and hypothermia; 2) tachypnea at 2–4 dpi and ataxic breathing with long-lasting apneas and hypercapnic hypoxemia at 6 dpi; and 3) viral replication in PBC NK1R neurons with NK1R-IR reduced by 75% and CASP3-IR colabeled at 6 dpi. Lethal H5N1 viral infection causes tachypnea at the early stage and ataxic breathing and apneas (hypercapnic hypoxemia) leading to death at the late stage. Its replication in the PBC induces apoptosis of local NK1R neurons, contributing to ataxic breathing and respiratory failure.

RT-PCR reveals muscarinic acetylcholine receptor mRNA in the pre-Bötzinger complex

2001 ◽  
Vol 281 (6) ◽  
pp. L1420-L1424 ◽  
Author(s):  
Jiunu Lai ◽  
Xuesi M. Shao ◽  
Richard W. Pan ◽  
Edward Dy ◽  
Cindy H. Huang ◽  
...  
Keyword(s):  
Muscarinic Receptor ◽  
Muscarinic Receptors ◽  
Respiratory Rhythm ◽  
Pcr Amplification ◽  
Cholinergic Receptor ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Muscarinic Receptor Subtypes ◽  
Rt Pcr ◽  
Bötzinger Complex

Muscarinic receptors mediate the postsynaptic excitatory effects of acetylcholine (ACh) on inspiratory neurons in the pre-Bötzinger complex (pre-BötC), the hypothesized site for respiratory rhythm generation. Because pharmacological tools for identifying the subtypes of the muscarinic receptors that underlie these effects are limited, we probed for mRNA for these receptors in the pre-BötC. We used RT-PCR to determine the expression of muscarinic receptor subtypes in tissue punches of the pre-BötC taken from rat medullary slices. Cholinergic receptor subtype M2 and M3 mRNAs were observed in the first round of PCR amplification. All five subtypes, M1–M5, were observed in the second round of amplification. Our results suggest that the majority of muscarinic receptor subtypes in the pre-BötC are M2 and M3, with minor expression of M1, M4, and M5.

Ionotropic excitatory amino acid receptors in pre-Bötzinger complex play a modulatory role in hypoxia-induced gasping in vivo

2004 ◽  
Vol 96 (5) ◽  
pp. 1643-1650 ◽  
Author(s):  
Irene C. Solomon
Keyword(s):  
Amino Acid ◽  
Excitatory Amino Acid ◽  
Respiratory Rhythm ◽  
Receptor Activation ◽  
Induced Response ◽  
Brain Hypoxia ◽  
Bötzinger Complex ◽  
Before And After ◽  
Additional Support

Activation of ionotropic excitatory amino acid (EAA) receptors in pre-Bötzinger complex (pre-BötC) not only influences the eupneic pattern of phrenic motor output but also modifies hypoxia-induced gasping in vivo by increasing gasp frequency. Although ionotropic EAA receptor activation in this region appears to be required for the generation of eupneic breathing, it remains to be determined whether similar activation is necessary for the production and/or expression of hypoxia-induced gasping. Therefore, we examined the effects of severe brain hypoxia before and after blockade of ionotropic EAA receptors in the pre-BötC in eight chloralose-anesthetized, deafferented, mechanically ventilated cats. In each experiment, before blockade of ionotropic EAA receptors in the pre-BötC, severe brain hypoxia (6% O2 in a balance of N2 for 3-6 min) produced gasping. Although bilateral microinjection of the broad-spectrum ionotropic EAA receptor antagonist kynurenic acid (20-100 mM; 40 nl) into the pre-BötC eliminated basal phrenic nerve discharge, severe brain hypoxia still produced gasping. Under these conditions, however, the onset latency to gasping was increased ( P < 0.05), the number of gasps was reduced for the same duration of hypoxic gas exposure ( P < 0.05), the duration of gasps was prolonged ( P < 0.05), and the duration between gasps was increased ( P < 0.05). These findings demonstrate that hypoxia-induced gasping in vivo does not require activation of ionotropic EAA receptors in the pre-BötC, but ionotropic EAA receptor activation in this region may modify the expression of the hypoxia-induced response. The present findings also provide additional support for the pre-BötC as the primary locus of respiratory rhythm generation.

Patterns of Phrenic Motor Output Evoked by Chemical Stimulation of Neurons Located in the Pre-Bötzinger Complex In Vivo

1999 ◽  
Vol 81 (3) ◽  
pp. 1150-1161 ◽  
Author(s):  
Irene C. Solomon ◽  
Norman H. Edelman ◽  
Judith A. Neubauer
Keyword(s):  
Short Duration ◽  
Respiratory Rhythm ◽  
High Amplitude ◽  
Chemical Stimulation ◽  
Arterial Blood ◽  
Bötzinger Complex ◽  
Tonic Excitation ◽  
Stimulation Of

Patterns of phrenic motor output evoked by chemical stimulation of neurons located in the pre-Bötzinger complex in vivo. The pre-Bötzinger complex (pre-BötC) has been proposed to be essential for respiratory rhythm generation from work in vitro. Much less, however, is known about its role in the generation and modulation of respiratory rhythm in vivo. Therefore we examined whether chemical stimulation of the in vivo pre-BötC manifests respiratory modulation consistent with a respiratory rhythm generator. In chloralose- or chloralose/urethan-anesthetized, vagotomized cats, we recorded phrenic nerve discharge and arterial blood pressure in response to chemical stimulation of neurons located in the pre-BötC with dl-homocysteic acid (DLH; 10 mM; 21 nl). In 115 of the 122 sites examined in the pre-BötC, unilateral microinjection of DLH produced an increase in phrenic nerve discharge that was characterized by one of the following changes in cycle timing and pattern: 1) a rapid series of high-amplitude, rapid rate of rise, short-duration bursts, 2) tonic excitation (with or without respiratory oscillations), 3) an integration of the first two types of responses (i.e., tonic excitation with high-amplitude, short-duration bursts superimposed), or 4) augmented bursts in the phrenic neurogram (i.e., eupneic breath ending with a high-amplitude, short-duration burst). In 107 of these sites, the phrenic neurogram response was accompanied by an increase or decrease (≥10 mmHg) in arterial blood pressure. Thus increases in respiratory burst frequency and production of tonic discharge of inspiratory output, both of which have been seen in vitro, as well as modulation of burst pattern can be produced by local perturbations of excitatory amino acid neurotransmission in the pre-BötC in vivo. These findings are consistent with the proposed role of this region as the locus for respiratory rhythm generation.

Small reduction of neurokinin-1 receptor-expressing neurons in the pre-Bötzinger complex area induces abnormal breathing periods in awake goats

2004 ◽  
Vol 97 (5) ◽  
pp. 1620-1628 ◽  
Author(s):  
J. M. Wenninger ◽  
L. G. Pan ◽  
L. Klum ◽  
T. Leekley ◽  
J. Bastastic ◽  
...  
Keyword(s):  
Eye Movement ◽  
Respiratory Muscle ◽  
Muscle Activation ◽  
Respiratory Rhythm ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Neurokinin 1 Receptor ◽  
Bötzinger Complex ◽  
Abnormal Breathing ◽  
Neurokinin 1

In awake rats, >80% bilateral reduction of neurokinin-1 receptor (NK1R)-expressing neurons in the pre-Bötzinger complex (pre-BötzC) resulted in hypoventilation and an “ataxic” breathing pattern (Gray PA, Rekling JC, Bocchiaro CM, Feldman JL, Science 286: 1566–1568, 1999). Accordingly, the present study was designed to gain further insight into the role of the pre-BötzC area NK1R-expressing neurons in the control of breathing during physiological conditions. Microtubules were chronically implanted bilaterally into the medulla of adult goats. After recovery from surgery, the neurotoxin saporin conjugated to substance P, specific for NK1R-expressing neurons, was bilaterally injected (50 pM in 10 μl) into the pre-BötzC area during the awake state ( n = 8). In unoperated goats, 34 ± 0.01% of the pre-BötzC area neurons are immunoreactive for the NK1R, but, in goats after bilateral injection of SP-SAP into the pre-BötzC area, NK1R immunoreactivity was reduced to 22.5 ± 2.5% (29% decrease, P < 0.01). Ten to fourteen days after the injection, the frequency of abnormal breathing periods was sixfold greater than before injection (107.8 ± 21.8/h, P < 0.001). Fifty-six percent of these periods were breaths of varying duration and volume with an altered respiratory muscle activation pattern, whereas the remaining were rapid, complete breaths with coordinated inspiratory-expiratory cycles. The rate of occurrence and characteristics of abnormal breathing periods were not altered during a CO2 inhalation-induced hyperpnea. Pathological breathing patterns were eliminated during non-rapid eye movement sleep in seven of eight goats, but they frequently occurred on arousal from non-rapid eye movement sleep. We conclude that a moderate reduction in pre-BötzC NK1R-expressing neurons results in state-dependent transient changes in respiratory rhythm and/or eupneic respiratory muscle activation patterns.

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