Disturbance of neural respiratory control in neonatal mice lacking gaba synthesizing enzyme 67-kda isoform of glutamic acid decarboxylase

Kuwana, Shun-ichi; Okada, Yasumasa; Sugawara, Yoshiko; Tsunekawa, Naoko; Obata, Kunihiko

doi:10.1016/s0306-4522(03)00338-5

Cited by 44 publications

(35 citation statements)

References 46 publications

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“…Furthermore, mutant mouse models lacking substantial populations of GABAergic and glycinergic medullary neurons have a lethal respiratory phenotype (Kuwana et al, 2003;Fujii et al, 2007), consistent with what we observed with our electrophysiolgocial recordings of Lbx1 mutants. Thus, we focused on examining inhibitory neurons within the NTS and the ventrolateral medulla, given that these regions are involved in modulating respiratory rhythm.…”

Section: Gabaergic and Glycinergic Inhibitory Inputssupporting

confidence: 90%

“…The loss of those actions may contribute to respiratory network and medullary structure abnormalities. Newborn mutant mice with deficiencies in GABA and glycine transmission have severely disrupted respiratory rhythm in vitro and in vivo (Kuwana et al, 2003;Fujii et al, 2007), similar to those generated by Lbx1 preparations lacking normal chloride-mediated neuromodulation during development.…”

Section: Reduction Of Gaba and Glycinergic Input From The Dorsolateramentioning

confidence: 77%

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Central Respiratory Rhythmogenesis Is Abnormal inLbx1- Deficient Mice

Pagliardini¹,

Ren²,

Gray³

et al. 2008

J. Neurosci.

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Lbx1 is a transcription factor that determines neuronal cell fate and identity in the developing medulla and spinal cord. Newborn Lbx1 mutant mice die of respiratory distress during the early postnatal period. Using in vitro brainstem-spinal cord preparations we tested the hypothesis that Lbx1 is necessary for the inception, development and modulation of central respiratory rhythmogenesis. The inception of respiratory rhythmogenesis at embryonic day 15 (E15) was not perturbed in Lbx1 mutant mice. However, the typical age-dependent increase in respiratory frequency observed in wild-type from E15 to P0 was not observed in Lbx1 mutant mice. The slow respiratory rhythms in E18.5 Lbx1 mutant preparations were increased to wild-type frequencies by application of substance P, thyrotropin releasing hormone, serotonin, noradrenaline, or the ampakine drug 1-(1,4-benzodioxan-6-yl-carbonyl) piperidine. Those data suggest that respiratory rhythm generation within the pre-Bötzinger complex (preBötC) is presumably functional in Lbx1 mutant mice with additional neurochemical drive. This was supported by anatomical data showing that the gross structure of the preBötC was normal, although there were major defects in neuronal populations that provide important modulatory drive to the preBötC including the retrotrapezoid nucleus, catecholaminergic brainstem nuclei, nucleus of the solitary tract, and populations of inhibitory neurons in the ventrolateral and dorsomedial medullary nuclei. Finally, we determined that those defects were caused by abnormalities of neuronal specification early in development or subsequent neuronal migration.

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Section: Gabaergic and Glycinergic Inhibitory Inputssupporting

confidence: 90%

Section: Reduction Of Gaba and Glycinergic Input From The Dorsolateramentioning

confidence: 77%

Central Respiratory Rhythmogenesis Is Abnormal inLbx1- Deficient Mice

Pagliardini¹,

Ren²,

Gray³

et al. 2008

J. Neurosci.

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“…Whole cell recordings demonstrated decreased firing of inspiratory neurons in the ventral medulla of GAD67 Ϫ/Ϫ mice. These data suggest that GABAergic transmission may be nonessential for respiratory rhythm generation but may contribute to maintain a regular respiratory rhythm and normal inspiratory pattern in neonatal mice (47).…”

Section: Mutant Newborn Mice With Abnormal Rhythmogenesismentioning

confidence: 82%

“…A role for GABA in the development of respiratory rhythm generation was looked for in null mutant newborn mice lacking the GABA-synthesizing enzyme 67-kDa glutamic acid decarboxylase (GAD67) (47). Irregular breathing and periodic gasplike respirations were noted.…”

Section: Mutant Newborn Mice With Abnormal Rhythmogenesismentioning

confidence: 99%

Neural control of breathing: insights from genetic mouse models

Gaultier¹,

Gallego²

2008

Journal of Applied Physiology

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“…Most HMs receive synaptic inhibition during inspiration and this inhibi-tion is presumed to be mediated by GABAergic premotor neurons that receive excitatory inspiratory drive (Sanchez et al 2009;Saywell and Feldman 2004). Disruption of GABA synthesis in neonatal mice leads to an irregular respiratory rhythm characterized by a short inspiratory period and a paucity of firing during the inspiratory phase in brain stem respiratory neurons (Kuwana et al 2003). Blocking GABA A receptors in the rhythmically active rat brain stem preparation leads to an increase in inspiratory burst frequency (Bou-Flores and Berger 2001).…”

Section: Introductionmentioning

confidence: 99%

GAD67-GFP+ Neurons in the Nucleus of Roller: A Possible Source of Inhibitory Input to Hypoglossal Motoneurons. I. Morphology and Firing Properties

Brederode

Yanagawa

Berger

2011

Journal of Neurophysiology

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van Brederode JFM, Yanagawa Y, Berger AJ. GAD67-GFPϩ neurons in the Nucleus of Roller: a possible source of inhibitory input to hypoglossal motoneurons. I. Morphology and firing properties. J Neurophysiol 105: 235-248, 2011. First published November 3, 2010 doi:10.1152/jn.00493.2010. In this study we examined the electrophysiological and morphological properties of inhibitory neurons located just ventrolateral to the hypoglossal motor (XII) nucleus in the Nucleus of Roller (NR). In vitro experiments were performed on medullary slices derived from postnatal day 5 (P5) to P15 GAD67-GFP knock-in mouse pups. ON cell recordings from GFPϩ cells in NR in rhythmic slices revealed that these neurons are spontaneously active, although their spiking activity does not exhibit inspiratory phase modulation. Morphologically, GFPϩ cells were bi-or multipolar cells with small-to medium-sized cell bodies and small dendritic trees that were often oriented parallel to the border of the XII nucleus. GFPϩ cells were classified as either tonic or phasic based on their firing responses to depolarizing step current stimulation in whole cell current clamp. Tonic GFPϩ cells fired a regular train of action potentials (APs) throughout the duration of the pulse and often showed rebound spikes after a hyperpolarizing step. In contrast, phasic GFPϩ neurons did not fire throughout the depolarizing current step but instead fired fewer than four APs at the onset of the pulse or fired multiple APs, but only after a marked delay. Phasic cells had a significantly smaller input resistance and shorter membrane time constant than tonic GFPϩ cells. In addition, phasic GFPϩ cells differed from tonic cells in the shape and time course of their spike afterpotentials, the minimum firing frequency at threshold current amplitude, and the slope of their current-frequency relationship. These results suggest that GABAergic neurons in the NR are morphologically and electrophysiologically heterogeneous cells that could provide tonic inhibitory synaptic input to HMs.

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Disturbance of neural respiratory control in neonatal mice lacking gaba synthesizing enzyme 67-kda isoform of glutamic acid decarboxylase

Cited by 44 publications

References 46 publications

Central Respiratory Rhythmogenesis Is Abnormal inLbx1- Deficient Mice

Central Respiratory Rhythmogenesis Is Abnormal inLbx1- Deficient Mice

Neural control of breathing: insights from genetic mouse models

GAD67-GFP+ Neurons in the Nucleus of Roller: A Possible Source of Inhibitory Input to Hypoglossal Motoneurons. I. Morphology and Firing Properties

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