scholarly journals Late-Expiratory Activity: Emergence and Interactions With the Respiratory CPG

2010 ◽  
Vol 104 (5) ◽  
pp. 2713-2729 ◽  
Author(s):  
Yaroslav I. Molkov ◽  
Ana P. L. Abdala ◽  
Bartholomew J. Bacak ◽  
Jeffrey C. Smith ◽  
Julian F. R. Paton ◽  
...  
Keyword(s):  
Computational Model ◽  
Brain Stem ◽  
Large Scale ◽  
Motor Pattern ◽  
Respiratory Rhythm ◽  
Oscillatory Activity ◽  
Published Data ◽  
Extended Model ◽  
Respiratory Network ◽  
Metabolic Conditions

The respiratory rhythm and motor pattern are hypothesized to be generated by a brain stem respiratory network with a rhythmogenic core consisting of neural populations interacting within and between the pre-Bötzinger (pre-BötC) and Bötzinger (BötC) complexes and controlled by drives from other brain stem compartments. Our previous large-scale computational model reproduced the behavior of this network under many different conditions but did not consider neural oscillations that were proposed to emerge within the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG) and drive preinspiratory (or late-expiratory, late-E) discharges in the abdominal motor output. Here we extend the analysis of our previously published data and consider new data on the generation of abdominal late-E activity as the basis for extending our computational model. The extended model incorporates an additional late-E population in RTN/pFRG, representing a source of late-E oscillatory activity. In the proposed model, under normal metabolic conditions, this RTN/pFRG oscillator is inhibited by BötC/pre-BötC circuits, and the late-E oscillations can be released by either hypercapnia-evoked activation of RTN/pFRG or by hypoxia-dependent suppression of RTN/pFRG inhibition by BötC/pre-BötC. The proposed interactions between BötC/pre-BötC and RTN/pFRG allow the model to reproduce several experimentally observed behaviors, including quantal acceleration of abdominal late-E oscillations with progressive hypercapnia and quantal slowing of phrenic activity with progressive suppression of pre-BötC excitability, as well as to predict a release of late-E oscillations by disinhibition of RTN/pFRG under normal conditions. The extended model proposes mechanistic explanations for the emergence of RTN/pFRG oscillations and their interaction with the brain stem respiratory network.

scholarly journals Testing the hypothesis of neurodegeneracy in respiratory network function with a priori transected arterially perfused brain stem preparation of rat

2016 ◽  
Vol 115 (5) ◽  
pp. 2593-2607 ◽  
Author(s):  
Sarah E. Jones ◽  
Mathias Dutschmann
Keyword(s):  
Brain Stem ◽  
A Priori ◽  
Respiratory Rhythm ◽  
High Amplitude ◽  
Respiratory Pattern ◽  
Network Function ◽  
Respiratory Network ◽  
Vagal Nerves ◽  
Motor Outputs ◽  
Lumbar Spinal

Degeneracy of respiratory network function would imply that anatomically discrete aspects of the brain stem are capable of producing respiratory rhythm. To test this theory we a priori transected brain stem preparations before reperfusion and reoxygenation at 4 rostrocaudal levels: 1.5 mm caudal to obex ( n = 5), at obex ( n = 5), and 1.5 ( n = 7) and 3 mm ( n = 6) rostral to obex. The respiratory activity of these preparations was assessed via recordings of phrenic and vagal nerves and lumbar spinal expiratory motor output. Preparations with a priori transection at level of the caudal brain stem did not produce stable rhythmic respiratory bursting, even when the arterial chemoreceptors were stimulated with sodium cyanide (NaCN). Reperfusion of brain stems that preserved the pre-Bötzinger complex (pre-BötC) showed spontaneous and sustained rhythmic respiratory bursting at low phrenic nerve activity (PNA) amplitude that occurred simultaneously in all respiratory motor outputs. We refer to this rhythm as the pre-BötC burstlet-type rhythm. Conserving circuitry up to the pontomedullary junction consistently produced robust high-amplitude PNA at lower burst rates, whereas sequential motor patterning across the respiratory motor outputs remained absent. Some of the rostrally transected preparations expressed both burstlet-type and regular PNA amplitude rhythms. Further analysis showed that the burstlet-type rhythm and high-amplitude PNA had 1:2 quantal relation, with burstlets appearing to trigger high-amplitude bursts. We conclude that no degenerate rhythmogenic circuits are located in the caudal medulla oblongata and confirm the pre-BötC as the primary rhythmogenic kernel. The absence of sequential motor patterning in a priori transected preparations suggests that pontine circuits govern respiratory pattern formation.

Invited Review: Neural network plasticity in respiratory control

2003 ◽  
Vol 94 (3) ◽  
pp. 1242-1252 ◽  
Author(s):  
K. F. Morris ◽  
D. M. Baekey ◽  
S. C. Nuding ◽  
T. E. Dick ◽  
R. Shannon ◽  
...  
Keyword(s):  
Brain Stem ◽  
Motor Pattern ◽  
Sleep Apnea Syndrome ◽  
Respiratory Rhythm ◽  
Respiratory Control ◽  
Sudden Infant Death ◽  
Sudden Infant ◽  
Cord Injury ◽  
Network Plasticity

Respiratory network plasticity is a modification in respiratory control that persists longer than the stimuli that evoke it or that changes the behavior produced by the network. Different durations and patterns of hypoxia can induce different types of respiratory memories. Lateral pontine neurons are required for decreases in respiratory frequency that follow brief hypoxia. Changes in synchrony and firing rates of ventrolateral and midline medullary neurons may contribute to the long-term facilitation of breathing after brief intermittent hypoxia. Long-term changes in central respiratory motor control may occur after spinal cord injury, and the brain stem network implicated in the production of the respiratory rhythm could be reconfigured to produce the cough motor pattern. Preliminary analysis suggests that elements of brain stem respiratory neural networks respond differently to hypoxia and hypercapnia and interact with areas involved in cardiovascular control. Plasticity or alterations in these networks may contribute to the chronic upregulation of sympathetic nerve activity and hypertension in sleep apnea syndrome and may also be involved in sudden infant death syndrome.

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.

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.

scholarly journals Neurogenic hypertension and the secrets of respiration

2017 ◽  
Vol 312 (6) ◽  
pp. R864-R872 ◽  
Author(s):  
Benedito H. Machado ◽  
Daniel B. Zoccal ◽  
Davi J. A. Moraes
Keyword(s):  
Brain Stem ◽  
Neural Control ◽  
Respiratory Rhythm ◽  
Sympathetic Outflow ◽  
Neurogenic Hypertension ◽  
Electrophysiological Properties ◽  
Respiratory Network ◽  
Rhythm Pattern ◽  
Contraction And Relaxation ◽  
The Brain

Despite recent advances in the knowledge of the neural control of cardiovascular function, the cause of sympathetic overactivity in neurogenic hypertension remains unknown. Studies from our laboratory point out that rats submitted to chronic intermittent hypoxia (CIH), an experimental model of neurogenic hypertension, present changes in the central respiratory network that impact the pattern of sympathetic discharge and the levels of arterial pressure. In addition to the fine coordination of respiratory muscle contraction and relaxation, which is essential for O2 and CO2 pulmonary exchanges, neurons of the respiratory network are connected precisely to the neurons controlling the sympathetic activity in the brain stem. This respiratory-sympathetic neuronal interaction provides adjustments in the sympathetic outflow to the heart and vasculature during each respiratory phase according to the metabolic demands. Herein, we report that CIH-induced sympathetic over activity and mild hypertension are associated with increased frequency discharge of ventral medullary presympathetic neurons. We also describe that their increased frequency discharge is dependent on synaptic inputs, mostly from neurons of the brain stem respiratory network, rather than changes in their intrinsic electrophysiological properties. In perspective, we are taking into consideration the possibility that changes in the central respiratory rhythm/pattern generator contribute to increased sympathetic outflow and the development of neurogenic hypertension. Our experimental evidence provides support for the hypothesis that changes in the coupling of respiratory and sympathetic networks might be one of the unrevealed secrets of neurogenic hypertension in rats.

scholarly journals An arterially perfused nose-olfactory bulb preparation of the rat

2015 ◽  
Vol 114 (3) ◽  
pp. 2033-2042 ◽  
Author(s):  
Fernando Pérez de los Cobos Pallarés ◽  
Davor Stanić ◽  
David Farmer ◽  
Mathias Dutschmann ◽  
Veronica Egger
Keyword(s):  
Olfactory Bulb ◽  
Brain Stem ◽  
Respiratory Rhythm ◽  
Oscillatory Activity ◽  
Patch Clamp Recording ◽  
Network Activation ◽  
In Situ Preparation ◽  
Oscillatory Power ◽  
Characteristic Features

A main feature of the mammalian olfactory bulb network is the presence of various rhythmic activities, in particular, gamma, beta, and theta oscillations, with the latter coupled to the respiratory rhythm. Interactions between those oscillations as well as the spatial distribution of network activation are likely to determine olfactory coding. Here, we describe a novel semi-intact perfused nose-olfactory bulb-brain stem preparation in rats with both a preserved olfactory epithelium and brain stem, which could be particularly suitable for the study of oscillatory activity and spatial odor mapping within the olfactory bulb, in particular, in hitherto inaccessible locations. In the perfused olfactory bulb, we observed robust spontaneous oscillations, mostly in the theta range. Odor application resulted in an increase in oscillatory power in higher frequency ranges, stimulus-locked local field potentials, and excitation or inhibition of individual bulbar neurons, similar to odor responses reported from in vivo recordings. Thus our method constitutes the first viable in situ preparation of a mammalian system that uses airborne odor stimuli and preserves these characteristic features of odor processing. This preparation will allow the use of highly invasive experimental procedures and the application of techniques such as patch-clamp recording, high-resolution imaging, and optogenetics within the entire olfactory bulb.

scholarly journals Intermittent hypoxia-induced sensitization of central chemoreceptors contributes to sympathetic nerve activity during late expiration in rats

2011 ◽  
Vol 105 (6) ◽  
pp. 3080-3091 ◽  
Author(s):  
Yaroslav I. Molkov ◽  
Daniel B. Zoccal ◽  
Davi J. A. Moraes ◽  
Julian F. R. Paton ◽  
Benedito H. Machado ◽  
...  
Keyword(s):  
Brain Stem ◽  
Sympathetic Nerve ◽  
Intermittent Hypoxia ◽  
Ventrolateral Medulla ◽  
Retrotrapezoid Nucleus ◽  
Respiratory Network ◽  
Metabolic Conditions ◽  
Motor Nerves ◽  
Parafacial Respiratory Group ◽  
The Brain

Hypertension elicited by chronic intermittent hypoxia (CIH) is associated with elevated activity of the thoracic sympathetic nerve (tSN) that exhibits an enhanced respiratory modulation reflecting a strengthened interaction between respiratory and sympathetic networks within the brain stem. Expiration is a passive process except for special metabolic conditions such as hypercapnia, when it becomes active through phasic excitation of abdominal motor nerves (AbN) in late expiration. An increase in CO2 evokes late-expiratory (late-E) discharges phase-locked to phrenic bursts with the frequency increasing quantally as hypercapnia increases. In rats exposed to CIH, the late-E discharges synchronized in AbN and tSN emerge in normocapnia. To elucidate the possible neural mechanisms underlying these phenomena, we extended our computational model of the brain stem respiratory network by incorporating a population of presympathetic neurons in the rostral ventrolateral medulla that received inputs from the pons, medullary respiratory compartments, and retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG). Our simulations proposed that CIH conditioning increases the CO2 sensitivity of RTN/pFRG neurons, causing a reduction in both the CO2 threshold for emerging the late-E activity in AbN and tSN and the hypocapnic threshold for apnea. Using the in situ rat preparation, we have confirmed that CIH-conditioned rats under normal conditions exhibit synchronized late-E discharges in AbN and tSN similar to those observed in control rats during hypercapnia. Moreover, the hypocapnic threshold for apnea was significantly lowered in CIH-conditioned rats relative to that in control rats. We conclude that CIH may sensitize central chemoreception and that this significantly contributes to the neural impetus for generation of sympathetic activity and hypertension.

scholarly journals Surgery for Coagulopathy-Related Intracerebral Hemorrhage: Craniotomy vs. Minimally Invasive Neurosurgery

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 564
Author(s):  
Yen-Bo Liu ◽  
Lu-Ting Kuo ◽  
Chih-Hao Chen ◽  
Woon-Man Kung ◽  
Hsin-Hsi Tsai ◽  
...  
Keyword(s):  
Minimally Invasive ◽  
Intracerebral Hemorrhage ◽  
Functional Outcomes ◽  
Large Scale ◽  
Promising Result ◽  
Multivariable Logistic Regression Analysis ◽  
Published Data ◽  
Complication Rates ◽  
Minimally Invasive Neurosurgery ◽  
Reduction Of Mortality

Coagulopathy-related intracerebral hemorrhage (ICH) is life-threatening. Recent studies have shown promising results with minimally invasive neurosurgery (MIN) in the reduction of mortality and improvement of functional outcomes, but no published data have recorded the safety and efficacy of MIN for coagulopathy-related ICH. Seventy-five coagulopathy-related ICH patients were retrospectively reviewed to compare the surgical outcomes between craniotomy (n = 52) and MIN (n = 23). Postoperative rebleeding rates, morbidity rates, and mortality at 1 month were analyzed. Postoperative Glasgow Outcome Scale Extended (GOSE) and modified Rankin Scale (mRS) scores at 1 year were assessed for functional outcomes. Morbidity, mortality, and rebleeding rates were all lower in the MIN group than the craniotomy group (8.70% vs. 30.77%, 8.70% vs. 19.23%, and 4.35% vs. 23.08%, respectively). The 1-year GOSE score was significantly higher in the MIN group than the craniotomy group (3.96 ± 1.55 vs. 3.10 ± 1.59, p = 0.027). Multivariable logistic regression analysis also revealed that MIN contributed to improved GOSE (estimate: 0.99650, p = 0.0148) and mRS scores (estimate: −0.72849, p = 0.0427) at 1 year. MIN, with low complication rates and improved long-term functional outcome, is feasible and favorable for coagulopathy-related ICH. This promising result should be validated in a large-scale prospective study.

Brain stem – from general view to computational model based on switchboard rules of operation

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Włodzisław Duch ◽  
Dariusz Mikołajewski
Keyword(s):  
Brain Stem ◽  
Large Scale ◽  
Ionic Channels ◽  
General View ◽  
The Central Nervous System ◽  
Network States ◽  
Large Scale Simulations ◽  
Influence Of Noise ◽  
The Brain ◽  
Sufficient Precision

Abstract Despite great progress in understanding the functions and structures of the central nervous system (CNS) the brain stem remains one of the least understood systems. We know that the brain stem acts as a decision station preparing the organism to act in a specific way, but such functions are rather difficult to model with sufficient precision to replicate experimental data due to the scarcity of data and complexity of large-scale simulations of brain stem structures. The approach proposed in this article retains some ideas of previous models, and provides more precise computational realization that enables qualitative interpretation of the functions played by different network states. Simulations are aimed primarily at the investigation of general switching mechanisms which may be executed in brain stem neural networks, as far as studying how the aforementioned mechanisms depend on basic neural network features: basic ionic channels, accommodation, and the influence of noise.

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