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Chi-sang Poon - One of the best experts on this subject based on the ideXlab platform.
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bidirectional plasticity of pontine Pneumotaxic postinspiratory drive implication for a pontomedullary respiratory central pattern generator
Progress in Brain Research, 2014Co-Authors: Chi-sang Poon, Gang SongAbstract:Abstract The “Pneumotaxic Center” in the rostral dorsolateral pons as delineated by Lumsden nine decades ago is known to play an important role in promoting the inspiratory off-switch (IOS) for inspiratory–expiratory phase transition as a fail-safe mechanism for preventing apneusis in the absence of vagal input. Traditionally, the pontine Pneumotaxic mechanism has been thought to contribute a tonic descending input that lowers the IOS threshold in medullary respiratory central pattern generator (rCPG) circuits, but otherwise does not constitute part of the rCPG. Recent evidence indicates that descending input from the Kolliker-Fuse nucleus (KFN) within the Pneumotaxic Center is essential for gating the postinspiratory phase of the three-phase respiratory rhythm to control the IOS in vagotomized animals. A critical question arising is whether such a descending Pneumotaxic input from KFN that drives postinspiratory activity is tonic (null hypothesis) or rhythmic with postinspiratory phase modulation (alternative hypothesis). Here, we show that multifarious evidence reported in the literature collectively indicates that the descending Pneumotaxic input may exhibit NMDA receptor-dependent short-term plasticity in the form of a biphasic neural differentiator that bidirectionally and phase-selectively modulates postinspiratory phase duration in response to vagal and peripheral chemoreceptor inputs independent of the responses in inspiratory and late-expiratory activities. The phase-selectivity property of the descending Pneumotaxic input implicates a population of pontine early-expiratory (postinspiratory/expiratory-decrementing) neurons as the most likely neural correlate of the Pneumotaxic mechanism that drives post-I activity, suggesting that the pontine Pneumotaxic mechanism may be an integral part of a pontomedullary rCPG that underlies the three-phase respiratory rhythm.
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Mechanisms of respiratory-ventilator entrainment and its buffering by differentiator-type nonassociative learning.
2013Co-Authors: Shawna M. Macdonald, Chi-sang PoonAbstract:(Possible reciprocal connections for all paths are not shown.) In the absence of PEEP (top panel), phasic volume-related inputs entrain the respiratory rhythm generator (I-E) via the nucleus tractus solitarius (NTS) which also modulates the Pneumotaxic Center in dorsolateral pons (dl-pons). Immediately upon the application of PEEP (middle panel), tonic activities in the NTS and dl-pons elicit the Hering-Breuer reflex prolongation of expiration and shortening of inspiration, momentarily impairing entrainment. Finally, habituation of the NTS and desensitization of the Pneumotaxic Center (bottom panel) eventually buffer the effect of PEEP, restoring the respiratory rhythm. Sustained stimulation of dl-pons produces similar Hering-Breuer reflex and desensitization effects as PEEP.
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bilateral lesions of pontine kolliker fuse nuclei provoke apnea instead of apneusis in anesthetized adult rats
Advances in Experimental Medicine and Biology, 2010Co-Authors: Chi-sang Poon, Gang SongAbstract:The Kolliker-Fuse nucleus (KF) has been traditionally dubbed the “Pneumotaxic Center”. Here, we report that lesions of KF nuclei of bilateral pons caused apnea (complete cessation of phrenic discharge) instead of apneusis in urethane-anesthetized, vagotomized, paralyzed and ventilated adult rats. After bilateral lesions of KF nuclei with the neuroexcitotoxin kainic acid, phrenic discharge disappeared and no spontaneous recovery of phrenic discharge was observed for up to 3 hours. During the apnea, hypoxia or hypercapnia provoked transient rhythmic phrenic discharge. The present finding showed that the KF nucleus not only directly participates in inspiratory to expiratory phase switching, but also provides a vital excitatory drive that is requisite for the generation of inspiratory activity.
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Nonassociative learning promotes respiratory entrainment to mechanical ventilation
2007Co-Authors: Shawna M. Macdonald, Chi-sang PoonAbstract:Background. Patient-ventilator synchrony is a major concern in critical care and is influenced by phasic lung-volume feedback control of the respiratory rhythm. Routine clinical application of positive end-expiratory pressure (PEEP) introduces a tonic input which, if unopposed, might disrupt respiratory-ventilator entrainment through sustained activation of the vagally-mediated Hering-Breuer reflex. We suggest that this potential adverse effect may be averted by two differentiator forms of nonassociative learning (habituation and desensitization) of the Hering-Breuer reflex via pontomedullary pathways. Methodology/Principal Findings. We tested these hypotheses in 17 urethane-anesthetized adult Sprague-Dawley rats under controlled mechanical ventilation. Without PEEP, phrenic discharge was entrained 1:1 to the ventilator rhythm. Application of PEEP momentarily dampened the entrainment to higher ratios but this effect was gradually adapted by nonassociative learning. Bilateral electrolytic lesions of the Pneumotaxic Center weakened the adaptation to PEEP, whereas sustained stimulation of the Pneumotaxic Center weakened the entrainment independent of PEEP. In all cases, entrainment was abolished after vagotomy. Conclusions/Significance. Our results demonstrate an important functional role for Pneumotaxic desensitization and extra-pontine habituation of the Hering-Breuer reflex elicited by lung inflation: acting as buffers or high-pass filters against tonic vagal volume input, these differentiator forms of nonassociative learning help to restore respiratory-ventilator entrainment in the face of PEEP. Such central sites-specific habituation and desensitization of the Hering-Breuer reflex provide a useful experimental model of nonassociative learning in mammals that is of particula
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cytoarchitecture of Pneumotaxic integration of respiratory and nonrespiratory information in the rat
The Journal of Neuroscience, 2006Co-Authors: Gang Song, Chi-sang PoonAbstract:The “Pneumotaxic Center” in the Kolliker-Fuse and medial parabrachial nuclei of dorsolateral pons (dl-pons) plays an important role in respiratory phase switching, modulation of respiratory reflex, and rhythmogenesis. Recent electrophysiological and neural tracing data implicate additional Pneumotaxic nuclei in (and a broader role for) the dl-pons in integrating respiratory and nonrespiratory information. Here, we examined the cytoarchitecture of the greater Pneumotaxic Center and its integrating function by using combined extracellular recording and juxtacellular labeling of unit respiratory rhythmic neurons in dl-pons in urethane-anesthetized, vagotomized, paralyzed, and servo-ventilated adult Sprague Dawley rats. Perievent histogram analysis identified four major types of neuronal discharge patterns: inspiratory, expiratory (with three subdivisions), inspiratory–expiratory, and expiratory–inspiratory phase spanning, sometimes with mild tonic background activity. Most recorded neurons were localized in the Kolliker-Fuse and medial parabrachial nuclei, but some were also found in lateral parabrachial nucleus, intertrigeminal nucleus, principal trigeminal sensory nucleus, and supratrigeminal nucleus. The majority of labeled neurons had large and spatially extended dendritic trees that spanned several of these dl-pons subnuclei, often with terminal dendrites ending in the ventral spinocerebellar tract. The distal sections of the primary and higher-order dendrites exhibited rich varicosities, sometimes with dendritic spines. Axons of some labeled neurons were traced all the way to the ventrolateral pons (vl-pons). These findings extend and generalize the classical definition of the Pneumotaxic Center to include extensive somatic–axonal–dendritic integration of complex descending and ascending respiratory information as well as nociceptive and possibly musculoskeletal and trigeminal information in multiple dl-pons and vl-pons structures in the rat.
Gang Song - One of the best experts on this subject based on the ideXlab platform.
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bidirectional plasticity of pontine Pneumotaxic postinspiratory drive implication for a pontomedullary respiratory central pattern generator
Progress in Brain Research, 2014Co-Authors: Chi-sang Poon, Gang SongAbstract:Abstract The “Pneumotaxic Center” in the rostral dorsolateral pons as delineated by Lumsden nine decades ago is known to play an important role in promoting the inspiratory off-switch (IOS) for inspiratory–expiratory phase transition as a fail-safe mechanism for preventing apneusis in the absence of vagal input. Traditionally, the pontine Pneumotaxic mechanism has been thought to contribute a tonic descending input that lowers the IOS threshold in medullary respiratory central pattern generator (rCPG) circuits, but otherwise does not constitute part of the rCPG. Recent evidence indicates that descending input from the Kolliker-Fuse nucleus (KFN) within the Pneumotaxic Center is essential for gating the postinspiratory phase of the three-phase respiratory rhythm to control the IOS in vagotomized animals. A critical question arising is whether such a descending Pneumotaxic input from KFN that drives postinspiratory activity is tonic (null hypothesis) or rhythmic with postinspiratory phase modulation (alternative hypothesis). Here, we show that multifarious evidence reported in the literature collectively indicates that the descending Pneumotaxic input may exhibit NMDA receptor-dependent short-term plasticity in the form of a biphasic neural differentiator that bidirectionally and phase-selectively modulates postinspiratory phase duration in response to vagal and peripheral chemoreceptor inputs independent of the responses in inspiratory and late-expiratory activities. The phase-selectivity property of the descending Pneumotaxic input implicates a population of pontine early-expiratory (postinspiratory/expiratory-decrementing) neurons as the most likely neural correlate of the Pneumotaxic mechanism that drives post-I activity, suggesting that the pontine Pneumotaxic mechanism may be an integral part of a pontomedullary rCPG that underlies the three-phase respiratory rhythm.
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bilateral lesions of pontine kolliker fuse nuclei provoke apnea instead of apneusis in anesthetized adult rats
Advances in Experimental Medicine and Biology, 2010Co-Authors: Chi-sang Poon, Gang SongAbstract:The Kolliker-Fuse nucleus (KF) has been traditionally dubbed the “Pneumotaxic Center”. Here, we report that lesions of KF nuclei of bilateral pons caused apnea (complete cessation of phrenic discharge) instead of apneusis in urethane-anesthetized, vagotomized, paralyzed and ventilated adult rats. After bilateral lesions of KF nuclei with the neuroexcitotoxin kainic acid, phrenic discharge disappeared and no spontaneous recovery of phrenic discharge was observed for up to 3 hours. During the apnea, hypoxia or hypercapnia provoked transient rhythmic phrenic discharge. The present finding showed that the KF nucleus not only directly participates in inspiratory to expiratory phase switching, but also provides a vital excitatory drive that is requisite for the generation of inspiratory activity.
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cytoarchitecture of Pneumotaxic integration of respiratory and nonrespiratory information in the rat
The Journal of Neuroscience, 2006Co-Authors: Gang Song, Chi-sang PoonAbstract:The “Pneumotaxic Center” in the Kolliker-Fuse and medial parabrachial nuclei of dorsolateral pons (dl-pons) plays an important role in respiratory phase switching, modulation of respiratory reflex, and rhythmogenesis. Recent electrophysiological and neural tracing data implicate additional Pneumotaxic nuclei in (and a broader role for) the dl-pons in integrating respiratory and nonrespiratory information. Here, we examined the cytoarchitecture of the greater Pneumotaxic Center and its integrating function by using combined extracellular recording and juxtacellular labeling of unit respiratory rhythmic neurons in dl-pons in urethane-anesthetized, vagotomized, paralyzed, and servo-ventilated adult Sprague Dawley rats. Perievent histogram analysis identified four major types of neuronal discharge patterns: inspiratory, expiratory (with three subdivisions), inspiratory–expiratory, and expiratory–inspiratory phase spanning, sometimes with mild tonic background activity. Most recorded neurons were localized in the Kolliker-Fuse and medial parabrachial nuclei, but some were also found in lateral parabrachial nucleus, intertrigeminal nucleus, principal trigeminal sensory nucleus, and supratrigeminal nucleus. The majority of labeled neurons had large and spatially extended dendritic trees that spanned several of these dl-pons subnuclei, often with terminal dendrites ending in the ventral spinocerebellar tract. The distal sections of the primary and higher-order dendrites exhibited rich varicosities, sometimes with dendritic spines. Axons of some labeled neurons were traced all the way to the ventrolateral pons (vl-pons). These findings extend and generalize the classical definition of the Pneumotaxic Center to include extensive somatic–axonal–dendritic integration of complex descending and ascending respiratory information as well as nociceptive and possibly musculoskeletal and trigeminal information in multiple dl-pons and vl-pons structures in the rat.
Nancy L. Chamberlin - One of the best experts on this subject based on the ideXlab platform.
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kolliker fuse gabaergic and glutamatergic neurons project to distinct targets
The Journal of Comparative Neurology, 2017Co-Authors: Joel C Geerling, Shigefumi Yokota, Irma Rukhadze, Dan Roe, Nancy L. ChamberlinAbstract:The Kolliker-Fuse nucleus (KF) is known primarily for its respiratory function as the “Pneumotaxic Center” or “pontine respiratory group.” Considered part of the parabrachial (PB) complex, KF contains glutamatergic neurons that project to respiratory-related targets in the medulla and spinal cord (Yokota et al., 2007). Here we describe an unexpected population of neurons in the caudal KF and adjacent lateral crescent subnucleus (PBlc), which are GABAergic and have an entirely different pattern of projections than glutamatergic KF neurons. First, immunofluorescence, in situ hybridization, and Cre-reporter labeling revealed that many of these GABAergic neurons express FoxP2 in both rats and mice. Next, using Cre-dependent axonal tracing in Vgat-IRES-Cre and Vglut2-IRES-Cre mice we identified different projection patterns from GABAergic and glutamatergic neurons in this region. GABAergic neurons in KF and PBlc project heavily and almost exclusively to trigeminal sensory nuclei, with minimal projections to cardiorespiratory nuclei in the brainstem, and none to the spinal cord. In contrast, glutamatergic KF neurons project heavily to the autonomic, respiratory, and motor regions of the medulla and spinal cord previously identified as efferent targets mediating KF cardiorespiratory effects. These findings identify a novel, GABAergic subpopulation of KF/PB neurons with a distinct efferent projection pattern targeting the brainstem trigeminal sensory system. Rather than regulating breathing, we propose that these neurons influence vibrissal sensorimotor function. This article is protected by copyright. All rights reserved.
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Topographic organization of respiratory responses to glutamate microstimulation of the parabrachial nucleus in the rat
The Journal of Neuroscience, 1994Co-Authors: Nancy L. Chamberlin, Clifford B. SaperAbstract:The parabrachial complex, also known as the Pneumotaxic Center or pontine respiratory group, has long been recognized as an important participant in respiratory control. One line of evidence supporting this idea is the demonstration of changes in breathing pattern following injection of neuroactive substances into or near the parabrachial complex. However, it is not yet known exactly which cell groups and projections mediate those responses. In order to address this issue, we explored the topographic organization of respiratory responses to chemical stimulation of the parabrachial complex of the rat and examined the descending projections of the most sensitive sites. Injection of glutamate (5–100 pmol) at specific sites in or near the parabrachial nucleus produced three distinct site-specific response patterns. First, hyperpnea followed glutamate injection into far rostral and midcaudal areas of the Kolliker-Fuse nucleus and most of the lateral parabrachial nucleus, including the external lateral, central lateral, dorsal lateral, and superior lateral subnuclei. Threshold hyperpneic effects were manifested as single, deepened breaths of premature onset. Suprathreshold doses of glutamate at these locations produced tachypnea. Neurons in these sites projected to the ventral respiratory group in the ventrolateral medulla. Second, the most intense inspiratory facilitatory responses were seen at mid to rostral levels of the Kolliker-Fuse nucleus, near the ventrolateral tip of the superior cerebellar peduncle. Even at threshold doses of glutamate, exhalation was incomplete, resulting in a breathing pattern that resembled apneusis (an inspiratory cramp). This site contained an especially dense cluster of neurons that projected either to the ventrolateral medulla or to the dorsal respiratory group in the nucleus of the solitary tract, but not to both areas. The third type of response, decreases in respiratory rate, occurred following glutamate injection at the most lateral and ventral boundaries of the Kolliker- Fuse nucleus. The most sensitive apneic sites were not found in the parabrachial nucleus but along the dorsal and medial edge of the principal sensory trigeminal nucleus and extending ventrally between the sensory and motor trigeminal nuclei. Scattered neurons in these sites were retrogradely labeled from the ventral but not the dorsal respiratory group. These results indicate that there are anatomically and functionally distinct cell populations in and near the parabrachial complex that, when chemically stimulated, can produce specific and sometimes opposing effects on respiration. The predominant effect of lateral parabrachial stimulation is respiratory facilitation, while inhibitory effects are elicited by trigeminal injections of glutamate.
Mamoru Aoki - One of the best experts on this subject based on the ideXlab platform.
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axonal projections from the pontine parabrachial kolliker fuse nuclei to the botzinger complex as revealed by antidromic stimulation in cats
Advances in Experimental Medicine and Biology, 1998Co-Authors: Son Gang, Akihiko Watanabe, Mamoru AokiAbstract:The pontine parabrachial and Kolliker-Fuse nuclear complex (NPB-KF) has been assumed to be the anatomical location of the Pneumotaxic Center (11). It contains high density of respiratory neurons with various discharge patterns (3, 6). Destruction or electrical stimulation of this area is known to produce profound changes in the respiratory rhythm (5, 24, 25). It is suggested that the NPB-KF exerts its effects by specifically modulating the activity of the medullary inspiratory ‘off-switch’ mechanism, which terminates inspiration and ensures the phase transition from inspiration to expiration (8, 9). However, axonal projections from the NPB-KF to the medullary structures specifically involved in the inspiratory ‘off-switch’ effects have not been well delineated. Previous studies by us demonstrated that the nucleus raphe magnus, a structure involved in the inspiratory ‘off-switch’, received strong axonal projections from the NPB-KF area (1, 21, 22). Another possible neuron group which may transmit the function of the NPB-KF is the Botzinger complex (Bote). The Bot. c. is known as a group of expiratory neurons in the vicinity of the retrofacial nucleus (14, 19). Most of those neurons have an augmenting firing pattern and widespread inhibitory connections to the medullary inspiratory premotor neurons (10, 12, 18). Recent studies by Smith et al. (20) and us (23) with the retrograde WGA-HRP tracing method revealed that the Bot. c. received strong projections from the lateral NPB and the KF. These studies suggest that these projections are composed of axons from the pontine respiratory and/or non-respiratory neurons which would modulate the activities of expiratory neurons in the Bot. c.
L. I. Khozhai - One of the best experts on this subject based on the ideXlab platform.
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Distribution of GABAergic Neurons in the Nuclei of the Pneumotaxic Center in the Early Postnatal Period in Health and Prenatal Insufficiency of the Serotoninergic System in Rats
Neuroscience and Behavioral Physiology, 2015Co-Authors: L. I. KhozhaiAbstract:The aim of the present work was to study the distribution of GABAergic neurons in structures of the Pneumotaxic Center (medial subnucleus of the parabrachial complex and the Kolliker–Fuse nucleus) in health and in conditions of serotoninergic system insufficiency during the prenatal period of development in Wistar rats. Endogenous serotonin content was decreased in fetuses by inhibition of tryptophan hydroxylase with parachlorophenylalanine, which was given to females on day 16 of pregnancy. Specimens from the pons from experimental and control (intact) rat pups were investigated at early postnatal (days 5, 10, and 12) and juvenile (day 20) ages. Groups of 5–6 experimental and control rat pups were used at each time point. GABAergic neurons were detected using antibodies to its synthetic enzyme glutamate decarboxylase (GAD67). The results showed that the Kolliker–Fuse nucleus contained a population of GABAergic neurons during the early periods of postnatal development, the numbers of cells in this population persisting to juvenile age. The medial subnucleus of the parabrachial complex contained an insignificant number of GABAergic neurons at the early time points, with a slight increase by juvenile age, though neurons continued to give weak immune reactions. Serotonin deficiency in structures of the Pneumotaxic Center led to decreases in the number of GABAergic neurons and decreases in the numbers of GABAergic synapses and their accumulations. The decrease in serotonin during the prenatal period could induce impairments of inhibitory afferentation of the nuclei of the Pneumotaxic Center and changes in local inhibitory GABAergic networks in its nuclei, which could result in impairments to inhibitory processes in the structures of this Center.
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distribution of gabaergic neurons in Pneumotaxic Center nuclei in the early postnatal period in norm and in prenatal deficiency of serotoninergic system in rats
Morfologii︠a︡ (Saint Petersburg Russia), 2015Co-Authors: L. I. KhozhaiAbstract:The aim of this study was to determine the distribution of GABAergic neurons in Pneumotaxic Center structures (parabrachial complex medial subnucleus and Kolliker-Fuse nucleus) in norm and in deficiency of serotoninergic system during the prenatal period of development in Wistar rats. Reduction of endogenous serotonin levels in fetal rats was achieved by tryptophan hydroxylase inhibition with para-chlorophenylalanine (PCPA), which was administered to female rats on Day 16 of gestation. Material was obtained from the area of the pons from experimental and control (intact) rat pups at early postnatal (Days 5, 10 and 12) and juvenile (Day 20) periods. At each time point, 5-6 animals were studied from both experimental and control groups. To demonstrate GABAergic neurons, antibodies against glutamate decarboxylase (GAD-67), the enzyme involved in its synthesis, were used. The results have shown that Kolliker-Fuse nucleus contained a population of GABAergic neurons at early postnatal period, the size of which was preserved until juvenile age. In parabrachial complex medial subnucleus during the early postnatal period, a small number of GABAergic neurons was detected, which was somewhat increased by juvenile age. Serotonin deficiency in Pneumotaxic Center structures lead to a reduction of the numbers of GABAergic neurons, GABAergic synapses and their clusters. A reduction of serotonin levels during the prenatal period may cause the disturbances in the inhibitory afferent signaling of the Pneumotaxic Center nuclei and lead to the changes of local inhibitory GABAergic networks in its nuclei, resulting in the disturbances of the inhibitory processes in the Center structures.