The Experts below are selected from a list of 219 Experts worldwide ranked by ideXlab platform
Mathias Dutschmann - One of the best experts on this subject based on the ideXlab platform.
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the pontine Kolliker Fuse Nucleus gates facial hypoglossal and vagal upper airway related motor activity
Respiratory Physiology & Neurobiology, 2021Co-Authors: Mathias Dutschmann, Pedro Trevizanbau, Rishi R Dhingra, Tara G Bautista, Werner I FuruyaAbstract:The pontine Kolliker-Fuse Nucleus (KFn) is a core Nucleus of respiratory network that mediates the inspiratory-expiratory phase transition and gates eupneic motor discharges in the vagal and hypoglossal nerves. In the present study, we investigated whether the same KFn circuit may also gate motor activities that control the resistance of the nasal airway, which is of particular importance in rodents. To do so, we simultaneously recorded phrenic, facial, vagal and hypoglossal cranial nerve activity in an in situ perFused brainstem preparation before and after bilateral injection of the GABA-receptor agonist isoguvacine (50-70 nl, 10 mM) into the KFn (n = 11). Our results show that bilateral inhibition of the KFn triggers apneusis (prolonged inspiration) and abolished pre-inspiratory discharge of facial, vagal and hypoglossal nerves as well as post-inspiratory discharge in the vagus. We conclude that the KFn plays a critical role for the eupneic regulation of naso-pharyngeal airway patency and the potential functions of the KFn in regulating airway patency and orofacial behavior is discussed.
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reciprocal connectivity of the periaqueductal gray with the ponto medullary respiratory network in rat
Brain Research, 2021Co-Authors: Pedro Trevizanbau, Rishi R Dhingra, Davor Stanic, Werner I Furuya, Stuart B Mazzone, Mathias DutschmannAbstract:Synaptic 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 Kolliker-Fuse Nucleus (KFn, n = 5), medullary Botzinger (BotC, n = 3) and pre-Botzinger complexes (pre-BotC; n = 3), and the caudal raphe nuclei (n = 3), and quantified the descending connectivity of the PAG targeting these brainstem respiratory regions. CT-B injections in the KFn, pre-BotC, and caudal raphe, but not in the BotC, resulted in CT-B-labeled neurons that were predominantly located in the lateral and ventrolateral PAG columns. In turn, CT-B injections in the lateral and ventrolateral PAG columns (n = 4) produced the highest numbers of CT-B-labeled neurons in the KFn and far fewer numbers of labeled neurons in the pre-BotC, BotC, and caudal raphe. 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.
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forebrain projection neurons target functionally diverse respiratory control areas in the midbrain pons and medulla oblongata
The Journal of Comparative Neurology, 2021Co-Authors: Pedro Trevizanbau, Rishi R Dhingra, Davor Stanic, Werner I Furuya, Stuart B Mazzone, Mathias DutschmannAbstract:Eupnea is generated by neural circuits located in the ponto-medullary brainstem, but can be modulated by higher brain inputs which contribute to volitional control of breathing and the expression of orofacial behaviors, such as vocalization, sniffing, coughing, and swallowing. Surprisingly, the anatomical organization of descending inputs that connect the forebrain with the brainstem respiratory network remains poorly defined. We hypothesized that descending forebrain projections target multiple distributed respiratory control nuclei across the neuroaxis. To test our hypothesis, we made discrete unilateral microinjections of the retrograde tracer cholera toxin subunit B in the midbrain periaqueductal gray (PAG), the pontine Kolliker-Fuse Nucleus (KFn), the medullary Botzinger complex (BotC), pre-BotC, or caudal midline raphe nuclei. We quantified the regional distribution of retrogradely labeled neurons in the forebrain 12-14 days postinjection. Overall, our data reveal that descending inputs from cortical areas predominantly target the PAG and KFn. Differential forebrain regions innervating the PAG (prefrontal, cingulate cortices, and lateral septum) and KFn (rhinal, piriform, and somatosensory cortices) imply that volitional motor commands for vocalization are specifically relayed via the PAG, while the KFn may receive commands to coordinate breathing with other orofacial behaviors (e.g., sniffing, swallowing). Additionally, we observed that the limbic or autonomic (interoceptive) systems are connected to broadly distributed downstream bulbar respiratory networks. Collectively, these data provide a neural substrate to explain how volitional, state-dependent, and emotional modulation of breathing is regulated by the forebrain.
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reciprocal connectivity of the periaqueductal gray with the ponto medullary respiratory network in rat
bioRxiv, 2020Co-Authors: Pedro Trevizanbau, Rishi R Dhingra, Davor Stanic, Werner I Furuya, Stuart B Mazzone, Mathias DutschmannAbstract:Abstract Synaptic 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 Kolliker-Fuse Nucleus (KFn, n=5), medullary Botzinger (BotC, n=3) and pre-Botzinger complexes (pre-BotC; n=3), and the caudal raphe nuclei (n=3), and quantified the ascending and descending connectivity of the PAG. CT-B injections in the KFn, pre-BotC, and caudal raphe, but not in the BotC, 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-BotC and caudal raphe. 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. Highlights The lateral and ventrolateral PAG project to the primary respiratory network. The Kolliker-Fuse Nucleus shares the densest reciprocal connectivity with the PAG. The Botzinger complex appears to have very little connectivity with the PAG.
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forebrain projection neurons target functionally diverse respiratory control areas in the midbrain pons and medulla oblongata
bioRxiv, 2020Co-Authors: Pedro Trevizanbau, Rishi R Dhingra, Davor Stanic, Werner I Furuya, Stuart B Mazzone, Mathias DutschmannAbstract:Abstract Eupnea is generated by neural circuits located in the ponto-medullary brainstem, but can be modulated by higher brain inputs which contribute to volitional control of breathing and the expression of orofacial behaviors, such as vocalization, sniffing, coughing and swallowing. Surprisingly, the anatomical organization of descending inputs that connect the forebrain with the brainstem respiratory network remains poorly defined. We hypothesized that descending forebrain projections target multiple distributed respiratory control nuclei across the neuraxis. To test our hypothesis, we made discrete unilateral microinjections of the retrograde tracer Cholera toxin subunit B (CT-B) in the midbrain periaqueductal gray (PAG), the pontine Kolliker-Fuse Nucleus (KFn), the medullary Botzinger complex (BotC), pre-Botzinger complex (pre-BotC) or caudal midline raphe nuclei. We quantified the regional distribution of retrogradely-labeled neurons in the forebrain 12-14 days post-injection. Overall, our data reveals that descending inputs from cortical areas predominantly target the PAG and KFn. Differential forebrain regions innervating the PAG (prefrontal, cingulate cortices, and lateral septum) and KFn (rhinal, piriform, and somatosensory cortices) imply that volitional motor commands for vocalization are specifically relayed via the PAG, while the KFn may receive commands to coordinate breathing with other orofacial behaviors (e.g. sniffing, swallowing). Additionally, we observed that the limbic or autonomic (interoceptive) systems are connected to broadly distributed downstream bulbar respiratory networks. Collectively, these data provide a neural substrate to explain how volitional, state-dependent, and emotional modulation of breathing is regulated by the forebrain.
Pedro Trevizanbau - One of the best experts on this subject based on the ideXlab platform.
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the pontine Kolliker Fuse Nucleus gates facial hypoglossal and vagal upper airway related motor activity
Respiratory Physiology & Neurobiology, 2021Co-Authors: Mathias Dutschmann, Pedro Trevizanbau, Rishi R Dhingra, Tara G Bautista, Werner I FuruyaAbstract:The pontine Kolliker-Fuse Nucleus (KFn) is a core Nucleus of respiratory network that mediates the inspiratory-expiratory phase transition and gates eupneic motor discharges in the vagal and hypoglossal nerves. In the present study, we investigated whether the same KFn circuit may also gate motor activities that control the resistance of the nasal airway, which is of particular importance in rodents. To do so, we simultaneously recorded phrenic, facial, vagal and hypoglossal cranial nerve activity in an in situ perFused brainstem preparation before and after bilateral injection of the GABA-receptor agonist isoguvacine (50-70 nl, 10 mM) into the KFn (n = 11). Our results show that bilateral inhibition of the KFn triggers apneusis (prolonged inspiration) and abolished pre-inspiratory discharge of facial, vagal and hypoglossal nerves as well as post-inspiratory discharge in the vagus. We conclude that the KFn plays a critical role for the eupneic regulation of naso-pharyngeal airway patency and the potential functions of the KFn in regulating airway patency and orofacial behavior is discussed.
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reciprocal connectivity of the periaqueductal gray with the ponto medullary respiratory network in rat
Brain Research, 2021Co-Authors: Pedro Trevizanbau, Rishi R Dhingra, Davor Stanic, Werner I Furuya, Stuart B Mazzone, Mathias DutschmannAbstract:Synaptic 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 Kolliker-Fuse Nucleus (KFn, n = 5), medullary Botzinger (BotC, n = 3) and pre-Botzinger complexes (pre-BotC; n = 3), and the caudal raphe nuclei (n = 3), and quantified the descending connectivity of the PAG targeting these brainstem respiratory regions. CT-B injections in the KFn, pre-BotC, and caudal raphe, but not in the BotC, resulted in CT-B-labeled neurons that were predominantly located in the lateral and ventrolateral PAG columns. In turn, CT-B injections in the lateral and ventrolateral PAG columns (n = 4) produced the highest numbers of CT-B-labeled neurons in the KFn and far fewer numbers of labeled neurons in the pre-BotC, BotC, and caudal raphe. 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.
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forebrain projection neurons target functionally diverse respiratory control areas in the midbrain pons and medulla oblongata
The Journal of Comparative Neurology, 2021Co-Authors: Pedro Trevizanbau, Rishi R Dhingra, Davor Stanic, Werner I Furuya, Stuart B Mazzone, Mathias DutschmannAbstract:Eupnea is generated by neural circuits located in the ponto-medullary brainstem, but can be modulated by higher brain inputs which contribute to volitional control of breathing and the expression of orofacial behaviors, such as vocalization, sniffing, coughing, and swallowing. Surprisingly, the anatomical organization of descending inputs that connect the forebrain with the brainstem respiratory network remains poorly defined. We hypothesized that descending forebrain projections target multiple distributed respiratory control nuclei across the neuroaxis. To test our hypothesis, we made discrete unilateral microinjections of the retrograde tracer cholera toxin subunit B in the midbrain periaqueductal gray (PAG), the pontine Kolliker-Fuse Nucleus (KFn), the medullary Botzinger complex (BotC), pre-BotC, or caudal midline raphe nuclei. We quantified the regional distribution of retrogradely labeled neurons in the forebrain 12-14 days postinjection. Overall, our data reveal that descending inputs from cortical areas predominantly target the PAG and KFn. Differential forebrain regions innervating the PAG (prefrontal, cingulate cortices, and lateral septum) and KFn (rhinal, piriform, and somatosensory cortices) imply that volitional motor commands for vocalization are specifically relayed via the PAG, while the KFn may receive commands to coordinate breathing with other orofacial behaviors (e.g., sniffing, swallowing). Additionally, we observed that the limbic or autonomic (interoceptive) systems are connected to broadly distributed downstream bulbar respiratory networks. Collectively, these data provide a neural substrate to explain how volitional, state-dependent, and emotional modulation of breathing is regulated by the forebrain.
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reciprocal connectivity of the periaqueductal gray with the ponto medullary respiratory network in rat
bioRxiv, 2020Co-Authors: Pedro Trevizanbau, Rishi R Dhingra, Davor Stanic, Werner I Furuya, Stuart B Mazzone, Mathias DutschmannAbstract:Abstract Synaptic 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 Kolliker-Fuse Nucleus (KFn, n=5), medullary Botzinger (BotC, n=3) and pre-Botzinger complexes (pre-BotC; n=3), and the caudal raphe nuclei (n=3), and quantified the ascending and descending connectivity of the PAG. CT-B injections in the KFn, pre-BotC, and caudal raphe, but not in the BotC, 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-BotC and caudal raphe. 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. Highlights The lateral and ventrolateral PAG project to the primary respiratory network. The Kolliker-Fuse Nucleus shares the densest reciprocal connectivity with the PAG. The Botzinger complex appears to have very little connectivity with the PAG.
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forebrain projection neurons target functionally diverse respiratory control areas in the midbrain pons and medulla oblongata
bioRxiv, 2020Co-Authors: Pedro Trevizanbau, Rishi R Dhingra, Davor Stanic, Werner I Furuya, Stuart B Mazzone, Mathias DutschmannAbstract:Abstract Eupnea is generated by neural circuits located in the ponto-medullary brainstem, but can be modulated by higher brain inputs which contribute to volitional control of breathing and the expression of orofacial behaviors, such as vocalization, sniffing, coughing and swallowing. Surprisingly, the anatomical organization of descending inputs that connect the forebrain with the brainstem respiratory network remains poorly defined. We hypothesized that descending forebrain projections target multiple distributed respiratory control nuclei across the neuraxis. To test our hypothesis, we made discrete unilateral microinjections of the retrograde tracer Cholera toxin subunit B (CT-B) in the midbrain periaqueductal gray (PAG), the pontine Kolliker-Fuse Nucleus (KFn), the medullary Botzinger complex (BotC), pre-Botzinger complex (pre-BotC) or caudal midline raphe nuclei. We quantified the regional distribution of retrogradely-labeled neurons in the forebrain 12-14 days post-injection. Overall, our data reveals that descending inputs from cortical areas predominantly target the PAG and KFn. Differential forebrain regions innervating the PAG (prefrontal, cingulate cortices, and lateral septum) and KFn (rhinal, piriform, and somatosensory cortices) imply that volitional motor commands for vocalization are specifically relayed via the PAG, while the KFn may receive commands to coordinate breathing with other orofacial behaviors (e.g. sniffing, swallowing). Additionally, we observed that the limbic or autonomic (interoceptive) systems are connected to broadly distributed downstream bulbar respiratory networks. Collectively, these data provide a neural substrate to explain how volitional, state-dependent, and emotional modulation of breathing is regulated by the forebrain.
Werner I Furuya - One of the best experts on this subject based on the ideXlab platform.
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the pontine Kolliker Fuse Nucleus gates facial hypoglossal and vagal upper airway related motor activity
Respiratory Physiology & Neurobiology, 2021Co-Authors: Mathias Dutschmann, Pedro Trevizanbau, Rishi R Dhingra, Tara G Bautista, Werner I FuruyaAbstract:The pontine Kolliker-Fuse Nucleus (KFn) is a core Nucleus of respiratory network that mediates the inspiratory-expiratory phase transition and gates eupneic motor discharges in the vagal and hypoglossal nerves. In the present study, we investigated whether the same KFn circuit may also gate motor activities that control the resistance of the nasal airway, which is of particular importance in rodents. To do so, we simultaneously recorded phrenic, facial, vagal and hypoglossal cranial nerve activity in an in situ perFused brainstem preparation before and after bilateral injection of the GABA-receptor agonist isoguvacine (50-70 nl, 10 mM) into the KFn (n = 11). Our results show that bilateral inhibition of the KFn triggers apneusis (prolonged inspiration) and abolished pre-inspiratory discharge of facial, vagal and hypoglossal nerves as well as post-inspiratory discharge in the vagus. We conclude that the KFn plays a critical role for the eupneic regulation of naso-pharyngeal airway patency and the potential functions of the KFn in regulating airway patency and orofacial behavior is discussed.
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reciprocal connectivity of the periaqueductal gray with the ponto medullary respiratory network in rat
Brain Research, 2021Co-Authors: Pedro Trevizanbau, Rishi R Dhingra, Davor Stanic, Werner I Furuya, Stuart B Mazzone, Mathias DutschmannAbstract:Synaptic 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 Kolliker-Fuse Nucleus (KFn, n = 5), medullary Botzinger (BotC, n = 3) and pre-Botzinger complexes (pre-BotC; n = 3), and the caudal raphe nuclei (n = 3), and quantified the descending connectivity of the PAG targeting these brainstem respiratory regions. CT-B injections in the KFn, pre-BotC, and caudal raphe, but not in the BotC, resulted in CT-B-labeled neurons that were predominantly located in the lateral and ventrolateral PAG columns. In turn, CT-B injections in the lateral and ventrolateral PAG columns (n = 4) produced the highest numbers of CT-B-labeled neurons in the KFn and far fewer numbers of labeled neurons in the pre-BotC, BotC, and caudal raphe. 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.
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forebrain projection neurons target functionally diverse respiratory control areas in the midbrain pons and medulla oblongata
The Journal of Comparative Neurology, 2021Co-Authors: Pedro Trevizanbau, Rishi R Dhingra, Davor Stanic, Werner I Furuya, Stuart B Mazzone, Mathias DutschmannAbstract:Eupnea is generated by neural circuits located in the ponto-medullary brainstem, but can be modulated by higher brain inputs which contribute to volitional control of breathing and the expression of orofacial behaviors, such as vocalization, sniffing, coughing, and swallowing. Surprisingly, the anatomical organization of descending inputs that connect the forebrain with the brainstem respiratory network remains poorly defined. We hypothesized that descending forebrain projections target multiple distributed respiratory control nuclei across the neuroaxis. To test our hypothesis, we made discrete unilateral microinjections of the retrograde tracer cholera toxin subunit B in the midbrain periaqueductal gray (PAG), the pontine Kolliker-Fuse Nucleus (KFn), the medullary Botzinger complex (BotC), pre-BotC, or caudal midline raphe nuclei. We quantified the regional distribution of retrogradely labeled neurons in the forebrain 12-14 days postinjection. Overall, our data reveal that descending inputs from cortical areas predominantly target the PAG and KFn. Differential forebrain regions innervating the PAG (prefrontal, cingulate cortices, and lateral septum) and KFn (rhinal, piriform, and somatosensory cortices) imply that volitional motor commands for vocalization are specifically relayed via the PAG, while the KFn may receive commands to coordinate breathing with other orofacial behaviors (e.g., sniffing, swallowing). Additionally, we observed that the limbic or autonomic (interoceptive) systems are connected to broadly distributed downstream bulbar respiratory networks. Collectively, these data provide a neural substrate to explain how volitional, state-dependent, and emotional modulation of breathing is regulated by the forebrain.
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reciprocal connectivity of the periaqueductal gray with the ponto medullary respiratory network in rat
bioRxiv, 2020Co-Authors: Pedro Trevizanbau, Rishi R Dhingra, Davor Stanic, Werner I Furuya, Stuart B Mazzone, Mathias DutschmannAbstract:Abstract Synaptic 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 Kolliker-Fuse Nucleus (KFn, n=5), medullary Botzinger (BotC, n=3) and pre-Botzinger complexes (pre-BotC; n=3), and the caudal raphe nuclei (n=3), and quantified the ascending and descending connectivity of the PAG. CT-B injections in the KFn, pre-BotC, and caudal raphe, but not in the BotC, 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-BotC and caudal raphe. 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. Highlights The lateral and ventrolateral PAG project to the primary respiratory network. The Kolliker-Fuse Nucleus shares the densest reciprocal connectivity with the PAG. The Botzinger complex appears to have very little connectivity with the PAG.
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forebrain projection neurons target functionally diverse respiratory control areas in the midbrain pons and medulla oblongata
bioRxiv, 2020Co-Authors: Pedro Trevizanbau, Rishi R Dhingra, Davor Stanic, Werner I Furuya, Stuart B Mazzone, Mathias DutschmannAbstract:Abstract Eupnea is generated by neural circuits located in the ponto-medullary brainstem, but can be modulated by higher brain inputs which contribute to volitional control of breathing and the expression of orofacial behaviors, such as vocalization, sniffing, coughing and swallowing. Surprisingly, the anatomical organization of descending inputs that connect the forebrain with the brainstem respiratory network remains poorly defined. We hypothesized that descending forebrain projections target multiple distributed respiratory control nuclei across the neuraxis. To test our hypothesis, we made discrete unilateral microinjections of the retrograde tracer Cholera toxin subunit B (CT-B) in the midbrain periaqueductal gray (PAG), the pontine Kolliker-Fuse Nucleus (KFn), the medullary Botzinger complex (BotC), pre-Botzinger complex (pre-BotC) or caudal midline raphe nuclei. We quantified the regional distribution of retrogradely-labeled neurons in the forebrain 12-14 days post-injection. Overall, our data reveals that descending inputs from cortical areas predominantly target the PAG and KFn. Differential forebrain regions innervating the PAG (prefrontal, cingulate cortices, and lateral septum) and KFn (rhinal, piriform, and somatosensory cortices) imply that volitional motor commands for vocalization are specifically relayed via the PAG, while the KFn may receive commands to coordinate breathing with other orofacial behaviors (e.g. sniffing, swallowing). Additionally, we observed that the limbic or autonomic (interoceptive) systems are connected to broadly distributed downstream bulbar respiratory networks. Collectively, these data provide a neural substrate to explain how volitional, state-dependent, and emotional modulation of breathing is regulated by the forebrain.
Rishi R Dhingra - One of the best experts on this subject based on the ideXlab platform.
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the pontine Kolliker Fuse Nucleus gates facial hypoglossal and vagal upper airway related motor activity
Respiratory Physiology & Neurobiology, 2021Co-Authors: Mathias Dutschmann, Pedro Trevizanbau, Rishi R Dhingra, Tara G Bautista, Werner I FuruyaAbstract:The pontine Kolliker-Fuse Nucleus (KFn) is a core Nucleus of respiratory network that mediates the inspiratory-expiratory phase transition and gates eupneic motor discharges in the vagal and hypoglossal nerves. In the present study, we investigated whether the same KFn circuit may also gate motor activities that control the resistance of the nasal airway, which is of particular importance in rodents. To do so, we simultaneously recorded phrenic, facial, vagal and hypoglossal cranial nerve activity in an in situ perFused brainstem preparation before and after bilateral injection of the GABA-receptor agonist isoguvacine (50-70 nl, 10 mM) into the KFn (n = 11). Our results show that bilateral inhibition of the KFn triggers apneusis (prolonged inspiration) and abolished pre-inspiratory discharge of facial, vagal and hypoglossal nerves as well as post-inspiratory discharge in the vagus. We conclude that the KFn plays a critical role for the eupneic regulation of naso-pharyngeal airway patency and the potential functions of the KFn in regulating airway patency and orofacial behavior is discussed.
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reciprocal connectivity of the periaqueductal gray with the ponto medullary respiratory network in rat
Brain Research, 2021Co-Authors: Pedro Trevizanbau, Rishi R Dhingra, Davor Stanic, Werner I Furuya, Stuart B Mazzone, Mathias DutschmannAbstract:Synaptic 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 Kolliker-Fuse Nucleus (KFn, n = 5), medullary Botzinger (BotC, n = 3) and pre-Botzinger complexes (pre-BotC; n = 3), and the caudal raphe nuclei (n = 3), and quantified the descending connectivity of the PAG targeting these brainstem respiratory regions. CT-B injections in the KFn, pre-BotC, and caudal raphe, but not in the BotC, resulted in CT-B-labeled neurons that were predominantly located in the lateral and ventrolateral PAG columns. In turn, CT-B injections in the lateral and ventrolateral PAG columns (n = 4) produced the highest numbers of CT-B-labeled neurons in the KFn and far fewer numbers of labeled neurons in the pre-BotC, BotC, and caudal raphe. 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.
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forebrain projection neurons target functionally diverse respiratory control areas in the midbrain pons and medulla oblongata
The Journal of Comparative Neurology, 2021Co-Authors: Pedro Trevizanbau, Rishi R Dhingra, Davor Stanic, Werner I Furuya, Stuart B Mazzone, Mathias DutschmannAbstract:Eupnea is generated by neural circuits located in the ponto-medullary brainstem, but can be modulated by higher brain inputs which contribute to volitional control of breathing and the expression of orofacial behaviors, such as vocalization, sniffing, coughing, and swallowing. Surprisingly, the anatomical organization of descending inputs that connect the forebrain with the brainstem respiratory network remains poorly defined. We hypothesized that descending forebrain projections target multiple distributed respiratory control nuclei across the neuroaxis. To test our hypothesis, we made discrete unilateral microinjections of the retrograde tracer cholera toxin subunit B in the midbrain periaqueductal gray (PAG), the pontine Kolliker-Fuse Nucleus (KFn), the medullary Botzinger complex (BotC), pre-BotC, or caudal midline raphe nuclei. We quantified the regional distribution of retrogradely labeled neurons in the forebrain 12-14 days postinjection. Overall, our data reveal that descending inputs from cortical areas predominantly target the PAG and KFn. Differential forebrain regions innervating the PAG (prefrontal, cingulate cortices, and lateral septum) and KFn (rhinal, piriform, and somatosensory cortices) imply that volitional motor commands for vocalization are specifically relayed via the PAG, while the KFn may receive commands to coordinate breathing with other orofacial behaviors (e.g., sniffing, swallowing). Additionally, we observed that the limbic or autonomic (interoceptive) systems are connected to broadly distributed downstream bulbar respiratory networks. Collectively, these data provide a neural substrate to explain how volitional, state-dependent, and emotional modulation of breathing is regulated by the forebrain.
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reciprocal connectivity of the periaqueductal gray with the ponto medullary respiratory network in rat
bioRxiv, 2020Co-Authors: Pedro Trevizanbau, Rishi R Dhingra, Davor Stanic, Werner I Furuya, Stuart B Mazzone, Mathias DutschmannAbstract:Abstract Synaptic 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 Kolliker-Fuse Nucleus (KFn, n=5), medullary Botzinger (BotC, n=3) and pre-Botzinger complexes (pre-BotC; n=3), and the caudal raphe nuclei (n=3), and quantified the ascending and descending connectivity of the PAG. CT-B injections in the KFn, pre-BotC, and caudal raphe, but not in the BotC, 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-BotC and caudal raphe. 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. Highlights The lateral and ventrolateral PAG project to the primary respiratory network. The Kolliker-Fuse Nucleus shares the densest reciprocal connectivity with the PAG. The Botzinger complex appears to have very little connectivity with the PAG.
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forebrain projection neurons target functionally diverse respiratory control areas in the midbrain pons and medulla oblongata
bioRxiv, 2020Co-Authors: Pedro Trevizanbau, Rishi R Dhingra, Davor Stanic, Werner I Furuya, Stuart B Mazzone, Mathias DutschmannAbstract:Abstract Eupnea is generated by neural circuits located in the ponto-medullary brainstem, but can be modulated by higher brain inputs which contribute to volitional control of breathing and the expression of orofacial behaviors, such as vocalization, sniffing, coughing and swallowing. Surprisingly, the anatomical organization of descending inputs that connect the forebrain with the brainstem respiratory network remains poorly defined. We hypothesized that descending forebrain projections target multiple distributed respiratory control nuclei across the neuraxis. To test our hypothesis, we made discrete unilateral microinjections of the retrograde tracer Cholera toxin subunit B (CT-B) in the midbrain periaqueductal gray (PAG), the pontine Kolliker-Fuse Nucleus (KFn), the medullary Botzinger complex (BotC), pre-Botzinger complex (pre-BotC) or caudal midline raphe nuclei. We quantified the regional distribution of retrogradely-labeled neurons in the forebrain 12-14 days post-injection. Overall, our data reveals that descending inputs from cortical areas predominantly target the PAG and KFn. Differential forebrain regions innervating the PAG (prefrontal, cingulate cortices, and lateral septum) and KFn (rhinal, piriform, and somatosensory cortices) imply that volitional motor commands for vocalization are specifically relayed via the PAG, while the KFn may receive commands to coordinate breathing with other orofacial behaviors (e.g. sniffing, swallowing). Additionally, we observed that the limbic or autonomic (interoceptive) systems are connected to broadly distributed downstream bulbar respiratory networks. Collectively, these data provide a neural substrate to explain how volitional, state-dependent, and emotional modulation of breathing is regulated by the forebrain.
Yukihiko Yasui - One of the best experts on this subject based on the ideXlab platform.
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orexinergic fibers are in contact with Kolliker Fuse Nucleus neurons projecting to the respiration related nuclei in the medulla oblongata and spinal cord of the rat
Brain Research, 2016Co-Authors: Shigefumi Yokota, Hirohiko Asano, Yukihiko YasuiAbstract:The neural pathways underlying the respiratory variation dependent on vigilance states remain unsettled. In the present study, we examined the orexinergic innervation of Kolliker-Fuse Nucleus (KFN) neurons sending their axons to the rostral ventral respiratory group (rVRG) and phrenic Nucleus (PhN) as well as to the hypoglossal Nucleus (HGN) by using a combined retrograde tracing and immunohistochemistry. After injection of cholera toxin B subunit (CTb) into the KFN, CTb-labeled neurons that are also immunoreactive for orexin (ORX) were found prominently in the perifornical and medial regions and additionally in the lateral region of the hypothalamic ORX field. After injection of fluorogold (FG) into the rVRG, PhN or HGN, we found an overlapping distribution of ORX-immunoreactive axon terminals and FG-labeled neurons in the KFN. Within the neuropil of the KFN, asymmetrical synaptic contacts were made between these terminals and neurons. We further demonstrated that many neurons labeled with FG injected into the rVRG, PhN, or HGN are immunoreactive for ORX receptor 2. Present data suggest that rVRG-, PhN- and HGN-projecting KFN neurons may be under the excitatory influence of the ORXergic neurons for the state-dependent regulation of respiration.
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glutamatergic Kolliker Fuse Nucleus neurons innervate hypoglossal motoneurons whose axons form the medial protruder branch of the hypoglossal nerve in the rat
Brain Research, 2011Co-Authors: Shigefumi Yokota, Toshiko Tsumori, Tatsuro Oka, Jianguo Niu, Yukihiko YasuiAbstract:Abstract This study was performed to understand the anatomical substrates for Kolliker–Fuse Nucleus (KFN) modulation of respiratory-related tongue movement. After application of cholera toxin B subunit (CTb) to the medial branch of the hypoglossal nerve (HGn) and injection of biotinylated dextran amine (BDA) into the KFN ipsilaterally, an overlapping distribution of BDA-labeled axon terminals and CTb-labeled neurons was found in the ventral compartment of the hypoglossal Nucleus (HGN) ipsilateral to the application and injection sites. At the electron microscopic level, the BDA-labeled terminals made asymmetrical synaptic contacts predominantly with dendrites of the HGN neurons, some of which were labeled with CTb. Using retrograde tracing combined with in situ hybridization, we demonstrated that almost all the KFN neurons sending their axons to the HGN were positive for vesicular glutamate transporter (VGLUT) 2 mRNA but not glutamic acid decarboxylase 67 mRNA. Using a combination of anterograde and retrograde tracing techniques and immunohistochemistry for VGLUT2, we further demonstrated that the KFN axon terminals with VGLUT2 immunoreactivity established close contact with the HGN motoneurons whose axons constitute the medial branch of the HGn. The present results suggest that glutamatergic KFN fibers may exert excitatory influence upon the HGN motoneurons sending their axons to the medial branch of the HGn for the control of protruder tongue muscles contraction to maintain airway patency during respiration.
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glutamatergic neurons in the Kolliker Fuse Nucleus project to the rostral ventral respiratory group and phrenic Nucleus a combined retrograde tracing and in situ hybridization study in the rat
Neuroscience Research, 2007Co-Authors: Shigefumi Yokota, Toshiko Tsumori, Tatsuro Oka, Sawako Nakamura, Yukihiko YasuiAbstract:Kolliker-Fuse Nucleus (KF) neurons are considered to excite motoneurons in the phrenic Nucleus (PhN) during inspiration through its projection to the PhN and/or to the rostral ventral respiratory group (rVRG), which in turn projects to the PhN, probably by releasing glutamate from their axon terminals. Using a combined retrograde tracing and in situ hybridization technique, here we demonstrate that most of the KF neurons projecting to the PhN and rVRG contain vesicular glutamate transporter 2 (VGLUT2) mRNA but not glutamic acid decarboxylase 67 (GAD67) mRNA, providing definitive evidence that these neurons are glutamatergic. Together with previous data by Stornetta et al. [Stornetta, R.L., Sevigny, C.P., Guyenet, P.G., 2003b. Inspiratory argumenting bulbospinal neurons express both glutamatergic and enkephalinergic phenotypes. J. Comp. Neurol. 455, 113-124], indicating that PhN-projecting rVRG neurons are VGLUT2 mRNA-positive, the present results suggest that the glutamatergic KF-PhN pathway and/or the glutamatergic KF-rVRG-PhN pathway transmit excitatory outputs of KF neurons to the PhN neurons during inspiration.
