The Experts below are selected from a list of 489 Experts worldwide ranked by ideXlab platform
Steven W Johnson - One of the best experts on this subject based on the ideXlab platform.
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potentiation of gabaa receptor agonists by gaba uptake inhibitors in the rat ventral midbrain
2001Co-Authors: Kezhong Shen, Steven W JohnsonAbstract:Abstract Whole-cell patch recordings were made from dopamine-containing neurons in the ventral tegmental area (VTA) and substantia nigra zona compacta (SNC). Isoguvacine evoked an outward current (at −60 mV) in a concentration-dependent manner with an EC 50 of 62±8 μM. The γ-aminobutyric acid (GABA) uptake inhibitor 1-(2(((diphenylmethylene)imino)oxy)ethyl)-1,2,5,6-tetrahydro-3-pyridine-carboxylic acid hydrochloride (NO 711) (3 μM) shifted the Isoguvacine concentration–response curve to the left, with a new EC 50 of 22±4 μM. l -Arginine (3 mM) also shifted the Isoguvacine concentration–response curve to the left, with a new EC 50 of 29±5 μM. l -Arginine (3 mM) increased the currents evoked by GABA (100 μM) and muscimol (1 μM) by 208% and 261%, respectively. The GABA uptake inhibitor 4,5,6,7,-tetrahydroisoxazolo[4,5- c ]-pyridin-3-ol hydrobromide (THPO) (300 μM) not only mimicked but also occluded the ability of l -arginine (3 mM) to potentiate currents evoked by Isoguvacine. Equimolar replacement of Na + with choline increased GABA-evoked currents, suggesting that a low Na + concentration has an inhibitory effect on GABA transport. Low Na + concentration (25 mM) inhibited Isoguvacine currents but still occluded the potentiating effects of l -arginine. We conclude that GABA uptake inhibitors potentiate the actions of the GABA A receptor agonists, Isoguvacine and muscimol, probably because they are effective substrates for GABA transporters in the ventral midbrain.
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bicuculline methiodide potentiates nmda dependent burst firing in rat dopamine neurons by blocking apamin sensitive ca2 activated k currents
1997Co-Authors: Steven W Johnson, Vincent SeutinAbstract:Abstract Apamin, a bee venom toxin which blocks a Ca 2+ -dependent K + current, potentiates N -methyl- d -aspartate (NMDA)-induced burst firing in dopamine neurons. We now report that burst firing is also potentiated by an apamin-like effect of bicuculline methiodide (BMI) at the same concentration (30 μ M) which blocks GABA A receptors in vitro. Using microelectrodes to record intracellularly from rat dopamine neurons in the midbrain slice, BMI reduced the apamin-sensitive afterhyperpolarization in all cells tested. BMI also mimicked apamin (100 nM) by potentiating burst firing produced by a concentration of NMDA (10 μ M) which is too low to evoke burst firing when perfused alone. When recording under voltage-clamp, both BMI and apamin reduced a depolarization-activated outward current which was also sensitive to perfusate containing no-added Ca 2+ . Although picrotoxin (100 μ M) and bicuculline free base (30 μ M) blocked the inhibition of firing produced by the GABA A agonist Isoguvacine (100 μ M), neither had apamin-like effects. We conclude that BMI potentiates burst firing by blocking an apamin-sensitive Ca 2+ -activated K + current.
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
2021Co-Authors: Mathias Dutschmann, Tara G Bautista, Pedro Trevizanbau, Rishi R Dhingra, 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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brainstem sources of cardiac vagal tone and respiratory sinus arrhythmia
2016Co-Authors: David G S Farmer, Mathias Dutschmann, Julian F. R. Paton, Anthony E Pickering, Robin M McallenAbstract:Key points Cardiac vagal tone is a strong predictor of health, although its central origins are unknown. Respiratory-linked fluctuations in cardiac vagal tone give rise to respiratory sinus arryhthmia (RSA), with maximum tone in the post-inspiratory phase of respiration. In the present study, we investigated whether respiratory modulation of cardiac vagal tone is intrinsically linked to post-inspiratory respiratory control using the unanaesthetized working heart-brainstem preparation of the rat. Abolition of post-inspiration, achieved by inhibition of the pontine Kolliker-Fuse nucleus, removed post-inspiratory peaks in efferent cardiac vagal activity and suppressed RSA, whereas substantial cardiac vagal tone persisted. After transection of the caudal pons, part of the remaining tone was removed by inhibition of nucleus of the solitary tract. We conclude that cardiac vagal tone depends upon at least 3 sites of the pontomedullary brainstem and that a significant proportion arises independently of RSA. Abstract Cardiac vagal tone is a strong predictor of health, although its central origins are unknown. The rat working heart-brainstem preparation shows strong cardiac vagal tone and pronounced respiratory sinus arrhythmia. In this preparation, recordings from the cut left cardiac vagal branch showed efferent activity that peaked in post-inspiration, ∼0.5 s before the cyclic minimum in heart rate (HR). We hypothesized that respiratory modulation of cardiac vagal tone and HR is intrinsically linked to the generation of post-inspiration. Neurons in the pontine Kolliker-Fuse nucleus (KF) were inhibited with bilateral microinjections of Isoguvacine (50–70 nl, 10 mm) to remove the post-inspiratory phase of respiration. This also abolished the post-inspiratory peak of cardiac vagal discharge (and cyclical HR modulation), although a substantial level of activity remained. In separate preparations with intact cardiac vagal branches but sympathetically denervated by thoracic spinal pithing, cardiac chronotropic vagal tone was quantified by HR compared to its final level after systemic atropine (0.5 μm). Bilateral KF inhibition removed 88% of the cyclical fluctuation in HR but, on average, only 52% of the chronotropic vagal tone. Substantial chronotropic vagal tone also remained after transection of the brainstem through the caudal pons. Subsequent bilateral Isoguvacine injections into the nucleus of the solitary tract further reduced vagal tone: remaining sources were untraced. We conclude that cardiac vagal tone depends on neurons in at least three sites of the pontomedullary brainstem, and much of it arises independently of respiratory sinus arrhythmia.
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inhibition of the pontine kolliker fuse nucleus abolishes eupneic inspiratory hypoglossal motor discharge in rat
2014Co-Authors: Tara G Bautista, Mathias DutschmannAbstract:The pontine Kolliker-Fuse nucleus (KF) has established functions in the regulation of inspiratory-expiratory phase transition and the regulation of upper airway patency via laryngeal valving mechanisms. Here we studied the role of the KF in the gating and modulation of eupneic hypoglossal motor activity (HNA) using the in situ perfused brainstem preparation, which displays robust inspiratory HNA. Microinjection of glutamate into the KF area triggered complex and often biphasic modulation (excitation/inhibition or inhibition/excitation) of HNA. Subsequent transient pharmacological inhibition of KF by unilateral microinjection of GABA-A receptor agonist Isoguvacine reduced HNA and while bilateral microinjections completely abolished HNA. Our results indicate that mixed and overlapping KF pre-motor neurons provide eupneic drive for inspiratory HNA and postinspiratory vagal nerve activity. Both motor activities have important functions in the regulation of upper airway patency during eupnea but also during various oro-pharyngeal behaviors. These results have potential implications in the contribution of state-dependent modulation of KF hypoglossal pre-motor neurons during sleep-wake cycle to obstructive sleep apnea.
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the kolliker fuse nucleus gates the postinspiratory phase of the respiratory cycle to control inspiratory off switch and upper airway resistance in rat
2006Co-Authors: Mathias Dutschmann, Horst HerbertAbstract:Lesion or pharmacological manipulation of the dorsolateral pons can transform the breathing pattern to apneusis (pathological prolonged inspiration). Apneusis reflects a disturbed inspiratory off-switch mechanism (IOS) leading to a delayed phase transition from inspiration to expiration. Under intact conditions the IOS is irreversibly mediated via activation of postinspiratory (PI) neurons within the respiratory network. In parallel, populations of laryngeal premotoneurons manifest the IOS by a brief glottal constriction during the PI phase. We investigated effects of pontine excitation (glutamate injection) or temporary lesion after injection of a GABA-receptor agonist (Isoguvacine) on the strength of PI-pool activity determined from respiratory motor outputs or kinesiological measurements of laryngeal resistance in a perfused brainstem preparation. Glutamate microinjections into distinct parts of the pontine Kolliker-Fuse nucleus (KF) evoked a tonic excitation of PI-motor activity or sustained laryngeal constriction accompanied by prolongation of the expiratory phase. Subsequent Isoguvacine microinjections at the same loci abolished PI-motor or laryngeal constrictor activity, triggered apneusis and established a variable and decreased breathing frequency. In summary, we revealed that excitation or inhibition of defined areas within the KF activated and blocked PI activity and, consequently, IOS. Therefore, we conclude, first, that descending KF inputs are essential to gate PI activity required for a proper pattern formation and phase control within the respiratory network, at least during absence of pulmonary stretch receptor activity and, secondly, that the KF contains large numbers of laryngeal PI premotor neurons that might have a key role in the regulation of upper airway resistance during reflex control and vocalization.
Vincent Seutin - One of the best experts on this subject based on the ideXlab platform.
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bicuculline methiodide potentiates nmda dependent burst firing in rat dopamine neurons by blocking apamin sensitive ca2 activated k currents
1997Co-Authors: Steven W Johnson, Vincent SeutinAbstract:Abstract Apamin, a bee venom toxin which blocks a Ca 2+ -dependent K + current, potentiates N -methyl- d -aspartate (NMDA)-induced burst firing in dopamine neurons. We now report that burst firing is also potentiated by an apamin-like effect of bicuculline methiodide (BMI) at the same concentration (30 μ M) which blocks GABA A receptors in vitro. Using microelectrodes to record intracellularly from rat dopamine neurons in the midbrain slice, BMI reduced the apamin-sensitive afterhyperpolarization in all cells tested. BMI also mimicked apamin (100 nM) by potentiating burst firing produced by a concentration of NMDA (10 μ M) which is too low to evoke burst firing when perfused alone. When recording under voltage-clamp, both BMI and apamin reduced a depolarization-activated outward current which was also sensitive to perfusate containing no-added Ca 2+ . Although picrotoxin (100 μ M) and bicuculline free base (30 μ M) blocked the inhibition of firing produced by the GABA A agonist Isoguvacine (100 μ M), neither had apamin-like effects. We conclude that BMI potentiates burst firing by blocking an apamin-sensitive Ca 2+ -activated K + current.
Roustem Khazipov - One of the best experts on this subject based on the ideXlab platform.
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timing of the developmental switch in gaba a mediated signaling from excitation to inhibition in ca3 rat hippocampus using gramicidin perforated patch and extracellular recordings
2007Co-Authors: Roman Tyzio, Roustem Khazipov, Gregory L. Holmes, Yehezkiel BenariAbstract:Summary: The timing of the developmental switch in the GABAA mediated responses from excitatory to inhibitory was studied in Wistar rat CA3 hippocampal pyramidal cells using gramicidin perforated patch-clamp and extracellular recordings. Gramicidin perforated patch recordings revealed a gradual developmental shift in the reversal potential of synaptic and Isoguvacine-induced GABAA mediated responses from –55 ± 4 mV at postnatal days P0–2 to −74 ± 3 mV at P13–15 with a midpoint of disappearance of the excitatory effects of GABA at around P8. Extracellular recordings in CA3 pyramidal cell layer revealed that the effect of Isoguvacine on multiple unit activity (MUA) switched from an increase to a decrease at around P10. The effect of synaptic GABAA mediated responses on MUA switched from an increase to a decrease at around P8. It is concluded that the developmental switch in the action of GABA via GABAA receptors from excitatory to inhibitory occurs in Wistar rat CA3 pyramidal cells at around P8–10, an age that coincides with the transition from immature to mature hippocampal rhythms. We propose that excitatory GABA contributes to enhanced excitability and ictogenesis in the neonatal rat hippocampus.
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Ca2+ oscillations mediated by the synergistic excitatory actions of GABA(A) and NMDA receptors in the neonatal hippocampus.
1997Co-Authors: Xavier Leinekugel, Igor Medina, Ilgham Khalilov, Yezekiel Ben-ari, Roustem KhazipovAbstract:We asked whether GABA(A) and NMDA receptors may act in synergy in neonatal hippocampal slices, at a time when GABA exerts a depolarizing action. The GABA(A) receptor agonist Isoguvacine reduced the voltage-dependent Mg2+ block of single NMDA channels recorded in cell-attached configuration from P(2-5) CA3 pyramidal neurons and potentiated the Ca2+ influx through NMDA channels. The synaptic response evoked by electrical stimulation of stratum radiatum was mediated by a synergistic interaction between GABA(A) and NMDA receptors. Network-driven Giant Depolarizing Potentials, which are a typical feature of the neonatal hippocampal network, provided coactivation of GABA(A) and NMDA receptors and were associated with spontaneous and synchronous Ca2+ increases in CA3 pyramidal neurons. Thus, at the early stages of development, GABA is a major excitatory transmitter that acts in synergy with NMDA receptors. This provides in neonatal neurons a hebbian stimulation that may be involved in neuronal plasticity and network formation in the developing hippocampus.
Tara G Bautista - 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
2021Co-Authors: Mathias Dutschmann, Tara G Bautista, Pedro Trevizanbau, Rishi R Dhingra, 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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inhibition of the pontine kolliker fuse nucleus abolishes eupneic inspiratory hypoglossal motor discharge in rat
2014Co-Authors: Tara G Bautista, Mathias DutschmannAbstract:The pontine Kolliker-Fuse nucleus (KF) has established functions in the regulation of inspiratory-expiratory phase transition and the regulation of upper airway patency via laryngeal valving mechanisms. Here we studied the role of the KF in the gating and modulation of eupneic hypoglossal motor activity (HNA) using the in situ perfused brainstem preparation, which displays robust inspiratory HNA. Microinjection of glutamate into the KF area triggered complex and often biphasic modulation (excitation/inhibition or inhibition/excitation) of HNA. Subsequent transient pharmacological inhibition of KF by unilateral microinjection of GABA-A receptor agonist Isoguvacine reduced HNA and while bilateral microinjections completely abolished HNA. Our results indicate that mixed and overlapping KF pre-motor neurons provide eupneic drive for inspiratory HNA and postinspiratory vagal nerve activity. Both motor activities have important functions in the regulation of upper airway patency during eupnea but also during various oro-pharyngeal behaviors. These results have potential implications in the contribution of state-dependent modulation of KF hypoglossal pre-motor neurons during sleep-wake cycle to obstructive sleep apnea.
