scholarly journals Generation and maintenance of the respiratory rhythm.

1982 ◽  
Vol 100 (1) ◽  
pp. 93-107 ◽  
Author(s):  
D W Richter
Keyword(s):  
Respiratory Rhythm ◽  
Active Stage ◽  
Ramp Generator ◽  
Respiratory Network ◽  
Loop Network ◽  
Respiratory Neurone ◽  
Medullary Respiratory Neurones ◽  
Intercostal Nerves ◽  
Discharge Patterns ◽  
Stage 1

Activities of the phrenic and internal intercostal nerves show that the central nervous rhythm of respiration consists of 3 phases: inspiratory, postinspiratory and expiratory. The discharge patterns of medullary respiratory neurones of the anaesthetized, paralysed cat can be correlated with these phases of the central respiratory cycle, and the postsynaptic activity of individual cells can be analysed to obtain information about the populations of neurones converging upon them. Inferences are drawn about respiratory neurone connectivity and a theory is developed that the respiratory network primarily employs inspiratory-related neurones and that medullary expiratory neurones are less important for the rhythmogenesis of respiration. It is suggested that the inspiratory network consists of a ramp generating excitatory loop network of interneurones whose discharge is brought to an end ('off-switched') by inhibitory late-inspiratory interneurones. The discharge pattern of the latter type of neurone is explained by inhibition arriving from early-inspiratory interneurones. Subsequent to 'off-switching' the ramp generator is assumed to be immediately gated by a very powerful postinspiratory inhibition whereas expiratory activity seems to be disfacilitated at this time. This is the period when 'passive' (stage 1) expiration occurs. Following this interposed postinspiratory phase 'active' (stage 2) expiration may begin, depending on the amount of excitatory inflow to the inspiratory ramp generator. When expiratory neurones are activated the inspiratory system is again synaptically inhibited and the frequency of ventilation is markedly slowed.

scholarly journals Reciprocal connectivity of the periaqueductal gray with the ponto-medullary respiratory network in rat

2020 ◽  
Author(s):  
Pedro Trevizan-Baú ◽  
Werner I. Furuya ◽  
Stuart B. Mazzone ◽  
Davor Stanić ◽  
Rishi R. Dhingra ◽  
...  
Keyword(s):  
Respiratory Rhythm ◽  
Upper Airway ◽  
Periaqueductal Gray ◽  
List Type ◽  
Airway Patency ◽  
Respiratory Network ◽  
Cholera Toxin Subunit B ◽  
Motor Activities ◽  
Descending Projections ◽  
Subunit B

AbstractSynaptic activities of the periaqueductal gray (PAG) can modulate or appropriate the respiratory motor activities in the context of behavior and emotion via descending projections to nucleus retroambiguus. However, alternative anatomical pathways for the mediation of PAG-evoked respiratory modulation via core nuclei of the brainstem respiratory network remains only partially described. We injected the retrograde tracer Cholera toxin subunit B (CT-B) in the pontine Kölliker-Fuse nucleus (KFn, n=5), medullary Bötzinger (BötC, n=3) and pre-Bötzinger complexes (pre-BötC; n=3), and the caudal raphé nuclei (n=3), and quantified the ascending and descending connectivity of the PAG. CT-B injections in the KFn, pre-BötC, and caudal raphé, but not in the BötC, resulted in CT-B-labeled neurons that were predominantly located in the lateral and ventrolateral PAG columns. In turn, CT-B injections into the lateral and ventrolateral PAG columns (n=4) yield the highest numbers of CT-B-labeled neurons in the KFn and far fewer numbers of labeled neurons in the pre-BötC and caudal raphé. Analysis of the relative projection strength revealed that the KFn shares the densest reciprocal connectivity with the PAG (ventrolateral and lateral columns, in particular). Overall, our data imply that the PAG may engage a distributed respiratory rhythm and pattern generating network beyond the nucleus retroambiguus to mediate downstream modulation of breathing. However, the reciprocal connectivity of the KFn and PAG suggests specific roles for synaptic interaction between these two nuclei that are most likely related to the regulation of upper airway patency during vocalization or other volitional orofacial behaviors.HighlightsThe lateral and ventrolateral PAG project to the primary respiratory network.The Kölliker-Fuse nucleus shares the densest reciprocal connectivity with the PAG.The Bötzinger complex appears to have very little connectivity with the PAG.

Reconfiguration of the Respiratory Network at the Onset of Locust Flight

1998 ◽  
Vol 80 (6) ◽  
pp. 3137-3147 ◽  
Author(s):  
Jan-Marino Ramirez
Keyword(s):  
Respiratory Activity ◽  
Respiratory Rhythm ◽  
Quiescent State ◽  
Suboesophageal Ganglion ◽  
Rhythm Generator ◽  
Locust Flight ◽  
Respiratory Network ◽  
Intracellular Stimulation ◽  
Tonic Stimulation ◽  
Stimulation Of

Ramirez, Jan-Marino. Reconfiguration of the respiratory network at the onset of locust flight. J. Neurophysiol. 80: 3137–3147, 1998. The respiratory interneurons 377, 378, 379 and 576 were identified within the suboesophageal ganglion (SOG) of the locust. Intracellular stimulation of these neurons excited the auxillary muscle 59 (M59), a muscle that is involved in the control of thoracic pumping in the locust. Like M59, these interneurons did not discharge during each respiratory cycle. However, the SOG interneurons were part of the respiratory rhythm generator because brief intracellular stimulation of these interneurons reset the respiratory rhythm and tonic stimulation increased the frequency of respiratory activity. At the onset of flight, the respiratory input into M59 and the SOG interneurons was suppressed, and these neurons discharged in phase with wing depression while abdominal pumping movements remained rhythmically active in phase with the slower respiratory rhythm (Fig. 9 ). The suppression of the respiratory input during flight seems to be mediated by the SOG interneuron 388. This interneuron was tonically activated during flight, and intracellular current injection suppressed the respiratory rhythmic input into M59. We conclude that the respiratory rhythm generator is reconfigured at flight onset. As part of the rhythm-generating network, the interneurons in the SOG are uncoupled from the rest of the respiratory network and discharge in phase with the flight rhythm. Because these SOG interneurons have a strong influence on thoracic pumping, we propose that this neural reconfiguration leads to a behavioral reconfiguration. In the quiescent state, thoracic pumping is coupled to the abdominal pumping movements and has auxillary functions. During flight, thoracic pumping is coupled to the flight rhythm and provides the major ventilatory movements during this energy-demanding locomotor behavior.

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 Aminophylline modulation of the mouse respiratory network changes during postnatal maturation

2000 ◽  
Vol 89 (5) ◽  
pp. 2015-2022 ◽  
Author(s):  
B. Wilken ◽  
J. M. Ramirez ◽  
F. Hanefeld ◽  
D. W. Richter
Keyword(s):  
Developmental Change ◽  
Respiratory Rhythm ◽  
Respiratory Control ◽  
Network Activity ◽  
Signal Pathways ◽  
Control Mechanisms ◽  
Patch Clamp Technique ◽  
Postnatal Maturation ◽  
Respiratory Network ◽  
Synaptic Drive

Aminophylline is a respiratory stimulant commonly used for the treatment of central apnea. Experiences from clinical practice, however, revealed that aminophylline is not reliably effective in preterm infants, whereas it is normally effective in infants and mature patients. In an established animal model for postnatal development of respiratory control mechanisms, we therefore examined the hypothesis that the clinical observations reflect a developmental change in the sensitivity of the central respiratory network to methylxanthines. The medullary respiratory network was isolated at different postnatal ages ( postnatal days 1–13; P1–P13) in a transverse mouse brain stem slice preparation. This preparation contains the pre-Bötzinger complex (PBC), a region that is critical for generation of respiratory rhythm. Spontaneous rhythmic respiratory activity was recorded from the hypoglossal (XII) rootlets and from neurons in the PBC by using the whole cell patch clamp technique. Bath-applied aminophylline [20 μM] increased the frequency (+41%) in neonatal animals (P1–P6) without affecting the amplitude of respiratory burst activity in XII rootlets. The same concentration of aminophylline did not have any significant effect on the frequency of respiratory XII bursts but increased the amplitude (+31%) in juvenile animals (P7–P13). In the same age group, aminophylline also augmented the amplitude and the duration of respiratory synaptic drive currents in respiratory PBC neurons. The data demonstrate that augmentation of the respiratory output is due to direct enhancement of central respiratory network activity and increase of synaptic drive of hypoglossal motoneurons in juvenile, but not neonatal, animals. This indicates a developmental change in the efficacy of aminophylline to reinforce central respiratory network activity. Therefore, we believe that the variable success in treating respiratory disturbances in premature infants reflects maturational changes in the expression of receptors and/or intracellular signal pathways in the central respiratory network.

scholarly journals Imaging of respiratory-related population activity with single-cell resolution

2007 ◽  
Vol 292 (1) ◽  
pp. C508-C516 ◽  
Author(s):  
Frank Funke ◽  
Mathias Dutschmann ◽  
Michael Müller
Keyword(s):  
Single Cell ◽  
Neuronal Activity ◽  
Single Cells ◽  
Activity Patterns ◽  
Respiratory Rhythm ◽  
Network Activity ◽  
Respiratory Neurons ◽  
Ventrolateral Medulla ◽  
Population Activity ◽  
Respiratory Network

The pre-Bötzinger complex (PBC) in the rostral ventrolateral medulla contains a kernel involved in respiratory rhythm generation. So far, its respiratory activity has been analyzed predominantly by electrophysiological approaches. Recent advances in fluorescence imaging now allow for the visualization of neuronal population activity in rhythmogenic networks. In the respiratory network, voltage-sensitive dyes have been used mainly, so far, but their low sensitivity prevents an analysis of activity patterns of single neurons during rhythmogenesis. We now have succeeded in using more sensitive Ca2+ imaging to study respiratory neurons in rhythmically active brain stem slices of neonatal rats. For the visualization of neuronal activity, fluo-3 was suited best in terms of neuronal specificity, minimized background fluorescence, and response magnitude. The tissue penetration of fluo-3 was improved by hyperosmolar treatment (100 mM mannitol) during dye loading. Rhythmic population activity was imaged with single-cell resolution using a sensitive charge-coupled device camera and a ×20 objective, and it was correlated with extracellularly recorded mass activity of the contralateral PBC. Correlated optical neuronal activity was obvious online in 29% of slices. Rhythmic neurons located deeper became detectable during offline image processing. Based on their activity patterns, 74% of rhythmic neurons were classified as inspiratory and 26% as expiratory neurons. Our approach is well suited to visualize and correlate the activity of several single cells with respiratory network activity. We demonstrate that neuronal synchronization and possibly even network configurations can be analyzed in a noninvasive approach with single-cell resolution and at frame rates currently not reached by most scanning-based imaging techniques.

Lack of the Kir4.1 Channel Subunit Abolishes K+ Buffering Properties of Astrocytes in the Ventral Respiratory Group: Impact on Extracellular K+ Regulation

2006 ◽  
Vol 95 (3) ◽  
pp. 1843-1852 ◽  
Author(s):  
Clemens Neusch ◽  
Nestoras Papadopoulos ◽  
Michael Müller ◽  
Iris Maletzki ◽  
Stefan M. Winter ◽  
...  
Keyword(s):  
Fluorescent Protein ◽  
Respiratory Rhythm ◽  
Brain Slices ◽  
Physiological Role ◽  
Functional Expression ◽  
Network Activity ◽  
Early Postnatal Development ◽  
Ventral Respiratory Group ◽  
Respiratory Network ◽  
Green Fluorescent

Ongoing rhythmic neuronal activity in the ventral respiratory group (VRG) of the brain stem results in periodic changes of extracellular K+. To estimate the involvement of the weakly inwardly rectifying K+ channel Kir4.1 (KCNJ10) in extracellular K+ clearance, we examined its functional expression in astrocytes of the respiratory network. Kir4.1 was expressed in astroglial cells of the VRG, predominantly in fine astrocytic processes surrounding capillaries and in close proximity to VRG neurons. Kir4.1 expression was up-regulated during early postnatal development. The physiological role of astrocytic Kir4.1 was studied using mice with a null mutation in the Kir4.1 channel gene that were interbred with transgenic mice expressing the enhanced green fluorescent protein in their astrocytes. The membrane potential was depolarized in astrocytes of Kir4.1−/− mice, and Ba2+-sensitive inward K+ currents were diminished. Brain slices from Kir4.1−/− mice, containing the pre-Bötzinger complex, which generates a respiratory rhythm, did not show any obvious differences in rhythmic bursting activity compared with wild-type controls, indicating that the lack of Kir4.1 channels alone does not impair respiratory network activity. Extracellular K+ measurements revealed that Kir4.1 channels contribute to extracellular K+ regulation. Kir4.1 channels reduce baseline K+ levels, and they compensate for the K+ undershoot. Our data indicate that Kir4.1 channels 1) are expressed in perineuronal processes of astrocytes, 2) constitute the major part of the astrocytic Kir conductance, and 3) contribute to regulation of extracellular K+ in the 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.

Functional Imaging Reveals Respiratory Network Activity During Hypoxic and Opioid Challenge in the Neonate Rat Tilted Sagittal Slab Preparation

2007 ◽  
Vol 97 (3) ◽  
pp. 2283-2292 ◽  
Author(s):  
Benjamin J. Barnes ◽  
Chi-Minh Tuong ◽  
Nicholas M. Mellen
Keyword(s):  
Functional Imaging ◽  
Respiratory Rhythm ◽  
Network Activity ◽  
Respiratory Neurons ◽  
Respiratory Network ◽  
Burst Amplitude ◽  
Single Unit Recordings ◽  
Parafacial Respiratory Group ◽  
Neonate Rat ◽  
Respiratory Networks

In mammals, respiration-modulated networks are distributed rostrocaudally in the ventrolateral quadrant of the medulla. Recent studies have established that in neonate rodents, two spatially separate networks along this column—the parafacial respiratory group (pFRG) and the pre-Bötzinger complex (preBötC)—are hypothesized to be sufficient for respiratory rhythm generation, but little is known about the connectivity within or between these networks. To be able to observe how these networks interact, we have developed a neonate rat medullary tilted sagittal slab, which exposes one column of respiration-modulated neurons on its surface, permitting functional imaging with cellular resolution. Here we examined how respiratory networks responded to hypoxic challenge and opioid-induced depression. At the systems level, the sagittal slab was congruent with more intact preparations: hypoxic challenge led to a significant increase in respiratory period and inspiratory burst amplitude, consistent with gasping. At opioid concentrations sufficient to slow respiration, we observed periods at integer multiples of control, matching quantal slowing. Consistent with single-unit recordings in more intact preparations, respiratory networks were distributed bimodally along the rostrocaudal axis, with respiratory neurons concentrated at the caudal pole of the facial nucleus, and 350 microns caudally, at the level of the pFRG and the preBötC, respectively. Within these regions neurons active during hypoxia- and/or opioid-induced depression were ubiquitous and interdigitated. In particular, contrary to earlier reports, opiate-insensitive neurons were found at the level of the preBötC.

scholarly journals Functional Connectivity in the Pontomedullary Respiratory Network

2008 ◽  
Vol 100 (4) ◽  
pp. 1749-1769 ◽  
Author(s):  
Lauren S. Segers ◽  
Sarah C. Nuding ◽  
Thomas E. Dick ◽  
Roger Shannon ◽  
David M. Baekey ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Respiratory Rhythm ◽  
Ventrolateral Medulla ◽  
Phase Switching ◽  
Functional Connections ◽  
Neuron Populations ◽  
Respiratory Network ◽  
Cross Correlation Analysis ◽  
Respiratory Modulation ◽  
Phrenic Motoneuron

Current models propose that a neuronal network in the ventrolateral medulla generates the basic respiratory rhythm and that this ventrolateral respiratory column (VRC) is profoundly influenced by the neurons of the pontine respiratory group (PRG). However, functional connectivity among PRG and VRC neurons is poorly understood. This study addressed four model-based hypotheses: 1) the respiratory modulation of PRG neuron populations reflects paucisynaptic actions of multiple VRC populations; 2) functional connections among PRG neurons shape and coordinate their respiratory-modulated activities; 3) the PRG acts on multiple VRC populations, contributing to phase-switching; and 4) neurons with no respiratory modulation located in close proximity to the VRC and PRG have widely distributed actions on respiratory-modulated cells. Two arrays of microelectrodes with individual depth adjustment were used to record sets of spike trains from a total of 145 PRG and 282 VRC neurons in 10 decerebrate, vagotomized, neuromuscularly blocked, ventilated cats. Data were evaluated for respiratory modulation with respect to efferent phrenic motoneuron activity and short-timescale correlations indicative of paucisynaptic functional connectivity using cross-correlation analysis and the “gravity” method. Correlogram features were found for 109 (3%) of the 3,218 pairs composed of a PRG and a VRC neuron, 126 (12%) of the 1,043 PRG–PRG pairs, and 319 (7%) of the 4,340 VRC–VRC neuron pairs evaluated. Correlation linkage maps generated for the data support our four motivating hypotheses and suggest network mechanisms for proposed modulatory functions of the PRG.

Identification of Two Types of Inspiratory Pacemaker Neurons in the Isolated Respiratory Neural Network of Mice

2001 ◽  
Vol 86 (1) ◽  
pp. 104-112 ◽  
Author(s):  
Muriel Thoby-Brisson ◽  
Jan-Marino Ramirez
Keyword(s):  
Neural Network ◽  
Respiratory Rhythm ◽  
Network Activity ◽  
Pacemaker Activity ◽  
Patch Clamp Technique ◽  
Population Activity ◽  
Pacemaker Neurons ◽  
Whole Cell Patch Clamp ◽  
Respiratory Network ◽  
Bursting Activity

In the respiratory network of mice, we characterized with the whole cell patch-clamp technique pacemaker properties in neurons discharging in phase with inspiration. The respiratory network was isolated in a transverse brain stem slice containing the pre-Bötzinger complex (PBC), the presumed site for respiratory rhythm generation. After blockade of respiratory network activity with 6-cyano-7-nitroquinoxalene-2,3-dione (CNQX), 18 of 52 inspiratory neurons exhibited endogenous pacemaker activity, which was voltage dependent, could be reset by brief current injections and could be entrained by repetitive stimuli. In the pacemaker group ( n = 18), eight neurons generated brief bursts (0.43 ± 0.03 s) at a relatively high frequency (1.05 ± 0.12 Hz) in CNQX. These bursts resembled the bursts that these neurons generated in the intact network during the interval between two inspiratory bursts. Cadmium (200 μM) altered but did not eliminate this bursting activity, while 0.5 μM tetrodotoxin suppressed bursting activity. Another set of pacemaker neurons (10 of 18) generated in CNQX longer bursts (1.57 ± 0.07 s) at a lower frequency (0.35 ± 0.01 Hz). These bursts resembled the inspiratory bursts generated in the intact network in phase with the population activity. This bursting activity was blocked by 50–100 μM cadmium or 0.5 μM tetrodotoxin. We conclude that the respiratory neural network contains pacemaker neurons with two types of bursting properties. The two types of pacemaker activities might have different functions within the respiratory network.

Sign in / Sign up

Export Citation Format

Share Document