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Kunihiko Obata - One of the best experts on this subject based on the ideXlab platform.
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Morpho-physiological criteria divide dentate gyrus interneurons into classes
Hippocampus, 2013Co-Authors: Jonas A. Hosp, Yuchio Yanagawa, Kunihiko Obata, Michael Strüber, Imre Vida, Peter Jonas, Marlene BartosAbstract:GABAergic inhibitory interneurons control fundamental aspects of neuronal network function. Their functional roles are assumed to be defined by the identity of their input synapses, the architecture of their dendritic tree, the passive and active membrane properties and finally the nature of their postsynaptic targets. Indeed, interneurons display a high degree of morphological and physiological heterogeneity. However, whether their morphological and physiological characteristics are correlated and whether interneuron diversity can be described by a continuum of GABAergic cell types or by distinct classes has remained unclear. Here we perform a detailed morphological and physiological characterization of GABAergic cells in the dentate gyrus, the input region of the hippocampus. To achieve an unbiased and efficient sampling and classification we used knock-in mice expressing the enhanced green fluorescent protein (eGFP) in Glutamate Decarboxylase 67 (GAD67)-positive neurons and performed cluster analysis. We identified five interneuron classes, each of them characterized by a distinct set of anatomical and physiological parameters. Cross-correlation analysis further revealed a direct relation between morphological and physiological properties indicating that dentate gyrus interneurons fall into functionally distinct classes which may differentially control neuronal network activity. © 2013 The Authors. Hippocampus Published by Wiley Periodicals, Inc.
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Differential gene expression in migrating cortical interneurons during mouse forebrain development.
The Journal of comparative neurology, 2010Co-Authors: Clare Faux, Yuchio Yanagawa, Kunihiko Obata, Sonja Rakic, William Andrews, John G. ParnavelasAbstract:gamma-Aminobutyric acid (GABA)ergic interneurons play a vital role in modulating the activity of the cerebral cortex, and disruptions to their function have been linked to neurological disorders such as schizophrenia and epilepsy. These cells originate in the ganglionic eminences (GE) of the ventral telencephalon and undergo tangential migration to enter the cortex Currently, little is known about the signaling mechanisms that regulate interneuron migration. We therefore performed a microarray analysis comparing the changes in gene expression between the GABAergic interneurons that are actively migrating into the cortex with those in the GE. We were able to isolate pure populations of GABAergic cells by fluorescence-activated cell sorting of cortex and GE from embryonic brains of Glutamate Decarboxylase 67 (GAD67)-green fluorescent protein (GFP) transgenic mice Our microarray analysis identified a number of novel genes that were upregulated in migrating cortical interneurons at both E13.5 and E 15.5. Many of these genes have previously been shown to play a role in cell migration of both neuronal and non-neuronal cell types. In addition, several of the genes identified are involved in the regulation of migratory processes, such as neurite outgrowth, cell adhesion, and remodeling of the actin cytoskeleton and microtubule network. Moreover, quantitative polymerase chain reaction and in situ hybridization analyses confirmed that the expression of some of these genes is restricted to cortical interneurons. These data therefore provide a framework for future studies aimed at elucidating the complexities of interneuron migration and, in turn, may reveal important genes that are related to the development of specific neurological disorders. J. Comp Neurol 5 18:1232-1248, 2010 (C) 2009 Wiley-Liss, Inc
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Aire controls the differentiation program of thymic epithelial cells in the medulla for the establishment of self-tolerance
Journal of Experimental Medicine, 2008Co-Authors: Masashi Yano, Yuchio Yanagawa, Kunihiko Obata, Kentaro Maemura, Noriyuki Kuroda, Makiko Meguro-horike, Yumiko Nishikawa, Hiroshi Kiyonari, Satoru TakahashiAbstract:The roles of autoimmune regulator (Aire) in the expression of the diverse arrays of tissue-restricted antigen (TRA) genes from thymic epithelial cells in the medulla (medullary thymic epithelial cells [mTECs]) and in organization of the thymic microenvironment are enigmatic. We approached this issue by creating a mouse strain in which the coding sequence of green fluorescent protein (GFP) was inserted into the Aire locus in a manner allowing concomitant disruption of functional Aire protein expression. We found that Aire+ (i.e., GFP+) mTECs were the major cell types responsible for the expression of Aire-dependent TRA genes such as insulin 2 and salivary protein 1 , whereas Aire-independent TRA genes such as C-reactive protein and Glutamate Decarboxylase 67 were expressed from both Aire+ and Aire− mTECs. Remarkably, absence of Aire from mTECs caused morphological changes together with altered distribution of mTECs committed to Aire expression. Furthermore, we found that the numbers of mTECs that express involucrin, a marker for terminal epidermal differentiation, were reduced in Aire-deficient mouse thymus, which was associated with nearly an absence of Hassall's corpuscle-like structures in the medulla. Our results suggest that Aire controls the differentiation program of mTECs, thereby organizing the global mTEC integrity that enables TRA expression from terminally differentiated mTECs in the thymic microenvironment.
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Noradrenergic excitation of a subpopulation of GABAergic cells in the basolateral amygdala via both activation of nonselective cationic conductance and suppression of resting K+ conductance: A study using Glutamate Decarboxylase 67-green fluorescent
Neuroscience, 2008Co-Authors: K. Kaneko, Toshikazu Kakizaki, Nobuaki Tamamaki, H. Owada, Nobuko Kume, M. Totsuka, T. Yamamoto, Hiromu Yawo, Takeshi Yagi, Kunihiko ObataAbstract:GABAergic interneurons play central roles in the regulation of neuronal activity in the basolateral nucleus of the amygdala (BLA). They are also suggested to be the principal targets of the brainstem noradrenergic afferents which are involved in the enhancement of the BLA-related memory. In addition, behavioral stress has been shown to impair noradrenergic facilitation of GABAergic transmission. However, the noradrenaline (NA) effects in the BLA have not been differentiated among medium- to large-sized GABAergic neurons and principal cells, and remain to be elucidated in terms of their underlying mechanisms. Glutamate Decarboxylase 67 (GAD67) is a biosynthetic enzyme of GABA and is specifically expressed in GABAergic neurons. To facilitate the study of the NA effects on GABAergic neurons in live preparations, we generated GAD67–green fluorescent protein (GFP) knock-in mice, in which GFP was expressed under the control of an endogenous GAD67 gene promoter. Here, we show that GFP was specifically expressed in GABAergic neurons in the BLA of this GAD67–GFP knock-in mouse. Under whole-cell patch-clamp recordings in vitro, we identified a certain subpopulation of GABAergic neurons in the BLA chiefly on the basis of the electrophysiological properties. When depolarized by a current injection, these neurons, which are referred to as type A, generated action potentials at relatively low frequency. We found that NA directly excited type-A cells via α1-adrenoceptors, whereas its effects on the other types of neurons were negligible. Two ionic mechanisms were involved in this excitability: the activation of nonselective cationic conductance and the suppression of the resting K+ conductance. NA also increased the frequency of spontaneous IPSCs in the principal cells of the BLA. It is suggested that the NA-dependent excitation of type-A cells attenuates the BLA output for a certain period.
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GABA and synaptic inhibition of mouse cerebellum lacking Glutamate Decarboxylase 67.
Biochemical and biophysical research communications, 2008Co-Authors: Kunihiko Obata, Shigeyoshi Itohara, Nobuko Kume, Moritoshi Hirono, Yoshiya Kawaguchi, Yuchio YanagawaAbstract:Abstract γ-Aminobutyric acid (GABA) is a major inhibitory neurotransmitter and also presumed to be a neurotrophic factor. GABA is synthesized by Glutamate Decarboxylase (GAD). A mouse lacking a 67 kDa isoform of GAD (GAD67) has a reduced GABA level in its brain at birth and does not survive postnatally because of cleft palate. In this study, to investigate the functional and developmental roles of GABA in the postnatal cerebellum, selective GAD67 deletion was achieved using a Cre-loxP strategy. In this mouse, GABA level was reduced to 16–44% in the cerebellum but not in the cerebrum. Inhibitory synaptic transmission to Purkinje cells was seriously impaired. However, the morphology of Purkinje cells and the density of synaptic terminals in the cerebellar cortex appeared unaffected, suggesting that GABA does not participate in cerebellar development substantially.
Yuchio Yanagawa - One of the best experts on this subject based on the ideXlab platform.
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Loss of Glutamate Decarboxylase 67 in Somatostatin-Expressing Neurons Leads to Anxiety-Like Behavior and Alteration in the Akt/GSK3β Signaling Pathway.
Frontiers in behavioral neuroscience, 2019Co-Authors: Shigeo Miyata, Kazuyuki Fujihara, Toshikazu Kakizaki, Ryota Kumagaya, Kaori Wakamatsu, Yuchio YanagawaAbstract:Major depressive disorder (MDD) is a highly prevalent psychiatric disorder worldwide. Several lines of evidence suggest that the dysfunction of somatostatin (SOM) neurons is associated with the pathophysiology of MDD. Importantly, most SOM neurons are γ-aminobutyric acid (GABA) interneurons. However, whether the dysfunction of GABAergic neurotransmission from SOM neurons contributes to the pathophysiology of MDD remains elusive. To address this issue, we investigated the emotional behaviors and relevant molecular mechanism in mice lacking Glutamate Decarboxylase 67 (GAD67), an isoform of GABA-synthesizing enzyme, specifically in SOM neurons (SOM-GAD67 mice). The SOM-GAD67 mice exhibited anxiety-like behavior in the open-field test without an effect on locomotor activity. The SOM-GAD67 mice showed depression-like behavior in neither the forced swimming test nor the sucrose preference test. In addition, the ability to form contextual fear memory was normal in the SOM-GAD67 mice. Furthermore, the plasma corticosterone level was normal in the SOM-GAD67 mice both under baseline and stress conditions. The expression ratios of p-AktSer473/Akt and p-GSK3βSer9/GSK3β were decreased in the frontal cortex of SOM-GAD67 mice. Taken together, these data suggest that the loss of GAD67 from SOM neurons may lead to the development of anxiety-like but not depression-like states mediated by modification of Akt/GSK3β activities.
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loss of Glutamate Decarboxylase 67 in somatostatin expressing neurons leads to anxiety like behavior and alteration in the akt gsk3β signaling pathway
Frontiers in Behavioral Neuroscience, 2019Co-Authors: Shigeo Miyata, Kazuyuki Fujihara, Toshikazu Kakizaki, Ryota Kumagaya, Kaori Wakamatsu, Yuchio YanagawaAbstract:Major depressive disorder (MDD) is a highly prevalent psychiatric disorder worldwide. Several lines of evidence suggest that the dysfunction of somatostatin (SOM) neurons is associated with the pathophysiology of MDD. Importantly, most SOM neurons are γ-aminobutyric acid (GABA) interneurons. However, whether the dysfunction of GABAergic neurotransmission from SOM neurons contributes to the pathophysiology of MDD remains elusive. To address this issue, we investigated the emotional behaviors and relevant molecular mechanism in mice lacking Glutamate Decarboxylase 67 (GAD67), an isoform of GABA-synthesizing enzyme, specifically in SOM neurons (SOM-GAD67 mice). The SOM-GAD67 mice exhibited anxiety-like behavior in the open-field test without an effect on locomotor activity. The SOM-GAD67 mice showed depression-like behavior in neither the forced swimming test nor the sucrose preference test. In addition, the ability to form contextual fear memory was normal in the SOM-GAD67 mice. Furthermore, the plasma corticosterone level was normal in the SOM-GAD67 mice both under baseline and stress conditions. The expression ratios of p-AktSer473/Akt and p-GSK3βSer9/GSK3β were decreased in the frontal cortex of SOM-GAD67 mice. Taken together, these data suggest that the loss of GAD67 from SOM neurons may lead to the development of anxiety-like but not depression-like states mediated by modification of Akt/GSK3β activities.
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Alterations in hypoglossal motor neurons due to GAD67 and VGAT deficiency in mice
Experimental neurology, 2016Co-Authors: Matthew J. Fogarty, Yuchio Yanagawa, Refik Kanjhan, Peter G. Noakes, Mark C. BellinghamAbstract:There is an emerging body of evidence that glycinergic and GABAergic synaptic inputs onto motor neurons (MNs) help regulate the final number of MNs and axonal muscle innervation patterns. Using mutant Glutamate Decarboxylase 67 (GAD67) and vesicular inhibitory amino acid transporter (VGAT) deficient mice, we describe the effect that deficiencies of presynaptic GABAergic and/or glycinergic release have on the post-synaptic somato-dendritic structure of motor neurons, and the development of excitatory and inhibitory synaptic inputs to MNs. We use whole-cell patch clamp recording of synaptic currents in E18.5 hypoglossal MNs from brainstem slices, combined with dye-filling of these recorded cells with Neurobiotin™, high-resolution confocal imaging and 3-dimensional reconstructions. Hypoglossal MNs from GAD67- and VGAT-deficient mice display decreased inhibitory neurotransmission and increased excitatory synaptic inputs. These changes are associated with increased dendritic arbor length, increased complexity of dendritic branching, and increased density of spiny processes. Our results show that presynaptic release of inhibitory amino acid neurotransmitters are potent regulators of hypoglossal MN morphology and key regulators of synaptic inputs during this critical developmental time point.
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Co-expression of GAD67 and choline acetyltransferase in neurons in the mouse spinal cord: A focus on lamina X
Brain research, 2016Co-Authors: Jittima Gotts, Yuchio Yanagawa, Lucy Atkinson, Jim Deuchars, Susan A. DeucharsAbstract:Lamina X of the spinal cord is a functionally diverse area with roles in locomotion, autonomic control and processing of mechano and nociceptive information. It is also a neurochemically diverse region. However, the different populations of cells in lamina X remain to be fully characterised. To determine the co-localisation of the enzymes responsible for the production of GABA and acetylcholine (which play major roles in the spinal cord) in lamina X of the adult and juvenile mouse, we used a transgenic mouse expressing green fluorescent protein (GFP) in Glutamate Decarboxylase 67 (GAD67) neurons, combined with choline acetyltransferase (ChAT) immunohistochemistry. ChAT-immunoreactive (IR) and GAD67-GFP containing neurons were observed in lamina X of both adult and juvenile mice and in both age groups a population of cells containing both ChAT-IR and GAD67-GFP were observed in lumbar, thoracic and cervical spinal cord. Such dual labelled cells were predominantly located ventral to the central canal. Immunohistochemistry for vesicular acetylcholine transporter (VAChT) and GAD67 revealed a small number of double labelled terminals located lateral, dorsolateral and ventrolateral to the central canal. This study therefore describes in detail a population of ChAT-IR/GAD67-GFP neurons predominantly ventral to the central canal of the cervical, thoracic and lumbar spinal cord of adult and juvenile mice. These cells potentially correspond to a sub-population of the cholinergic central canal cluster cells which may play a unique role in controlling spinal cord circuitry.
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Corticofugal GABAergic projection neurons in the mouse frontal cortex.
Frontiers in Neuroanatomy, 2015Co-Authors: Ryohei Tomioka, Kenji Sakimura, Yuchio YanagawaAbstract:Cortical projection neurons are classified by hodology in corticocortical, commissural and corticofugal subtypes. Although cortical projection neurons had been regarded as only Glutamatergic neurons, recently corticocortical GABAergic projection neurons has been also reported in several species. Here, we demonstrate corticofugal GABAergic projection neurons in the mouse frontal cortex. We employed viral-vector-mediated anterograde tracing, classical retrograde tracing, and immunohistochemistry to characterize neocortical GABAergic projection neurons. Injections of the Cre-dependent adeno-associated virus into Glutamate Decarboxylase 67 (GAD67)-Cre knock-in mice revealed neocortical GABAergic projections widely to the forebrain, including the cerebral cortices, caudate putamen (CPu), ventral pallidum (VP), lateral globus pallidus (LGP), nucleus accumbens, and olfactory tubercle (Tu). Minor GABAergic projections were also found in the mediodorsal thalamic nucleus, diagonal band of Broca, medial globus pallidus, substantial nigra, and dorsal raphe nucleus. Retrograde tracing studies also demonstrated corticofugal GABAergic projection neurons in the mouse frontal cortex. Further immunohistochemical screening with neurochemical markers revealed the majority of corticostriatal GABAergic projection neurons were positive for somatostatin (SS)-immunoreactivity. In contrast, corticothalamic GABAergic projection neurons were not identified by representative neurochemical markers for GABAergic neurons. These findings suggest that corticofugal GABAergic projection neurons are heterogeneous in terms of their neurochemical properties and target nuclei, and provide axonal innervations mainly to the nuclei in the basal ganglia.
Naoko Tsunekawa - One of the best experts on this subject based on the ideXlab platform.
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experimental induction of palate shelf elevation in Glutamate Decarboxylase 67 deficient mice with cleft palate due to vertically oriented palatal shelf
Birth Defects Research Part A-clinical and Molecular Teratology, 2007Co-Authors: Sachiko Iseki, Naoko Tsunekawa, Yoko Yamada, Kazuhiro Eto, Masako Ishiisuzuki, Kunihiko ObataAbstract:BACKGROUND: Gamma-aminobutyric acid is an inhibitory neurotransmitter, synthesized by two isoforms of Glutamate Decarboxylase (GAD), GAD65 and -67. Unexpectedly, inactivation of GAD67 induces cleft palate in mice. Reduction of spontaneous tongue movement resulting from decreased motor nerve activity has been related to the development of cleft palate in GAD67−/− fetuses. In the present study, development of cleft palate was examined histologically and manipulated with culture of the maxilla and partial resection of fetal tongue. METHODS: GAD67−/− mice and their littermates were used. Histological examination and immunohistochemistry were performed conventionally. Organ culture of the maxilla was carried out as reported previously. Fetuses were maintained alive under anesthesia and tips of their tongues were resected. RESULTS: Elevation of palatal shelves, the second step of palate formation, was not observed in GAD67−/− mice. In wild-type mice, GAD67 and gamma-aminobutyric acid were not expressed in the palatal shelves, except in the medial edge epithelium. During 2 days of culture of maxillae dissected from E13.5–E14.0 GAD67−/− fetuses, elevation and fusion of the palatal shelves were induced. When E13.5–15.5 mutant fetuses underwent partial tongue resection, the palatal shelves became elevated within 30 min. CONCLUSIONS: These results suggest that the potential for palate formation is maintained in the palatal shelves of GAD67−/− fetuses, but it is obstructed by other, probably neural, factors, resulting in cleft palate. Birth Defects Research (Part A) 2007. © 2007 Wiley-Liss, Inc.
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Experimental induction of palate shelf elevation in Glutamate Decarboxylase 67‐deficient mice with cleft palate due to vertically oriented palatal shelf
Birth defects research. Part A Clinical and molecular teratology, 2007Co-Authors: Sachiko Iseki, Naoko Tsunekawa, Masako Ishii-suzuki, Yoko Yamada, Kazuhiro Eto, Kunihiko ObataAbstract:BACKGROUND: Gamma-aminobutyric acid is an inhibitory neurotransmitter, synthesized by two isoforms of Glutamate Decarboxylase (GAD), GAD65 and -67. Unexpectedly, inactivation of GAD67 induces cleft palate in mice. Reduction of spontaneous tongue movement resulting from decreased motor nerve activity has been related to the development of cleft palate in GAD67−/− fetuses. In the present study, development of cleft palate was examined histologically and manipulated with culture of the maxilla and partial resection of fetal tongue. METHODS: GAD67−/− mice and their littermates were used. Histological examination and immunohistochemistry were performed conventionally. Organ culture of the maxilla was carried out as reported previously. Fetuses were maintained alive under anesthesia and tips of their tongues were resected. RESULTS: Elevation of palatal shelves, the second step of palate formation, was not observed in GAD67−/− mice. In wild-type mice, GAD67 and gamma-aminobutyric acid were not expressed in the palatal shelves, except in the medial edge epithelium. During 2 days of culture of maxillae dissected from E13.5–E14.0 GAD67−/− fetuses, elevation and fusion of the palatal shelves were induced. When E13.5–15.5 mutant fetuses underwent partial tongue resection, the palatal shelves became elevated within 30 min. CONCLUSIONS: These results suggest that the potential for palate formation is maintained in the palatal shelves of GAD67−/− fetuses, but it is obstructed by other, probably neural, factors, resulting in cleft palate. Birth Defects Research (Part A) 2007. © 2007 Wiley-Liss, Inc.
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Development of spontaneous mouth/tongue movement and related neural activity, and their repression in fetal mice lacking Glutamate Decarboxylase 67
The European journal of neuroscience, 2005Co-Authors: Naoko Tsunekawa, Akiko Arata, Kunihiko ObataAbstract:Spontaneous body movement starts at early fetal stage, at embryonic day (E) 12-15 in mice. In the present study, the movement of the head region was studied in E13-14 mice by in utero ultrasound imaging, together with the in vitro recording of underlying neural activities in the hypoglossal nerve and the ventral root of the upper cervical cord of an isolated brainstem-spinal cord preparation. The role of gamma-aminobutyric acid (GABA) in the generation of fetal movement was assessed using mice lacking GABA-synthesizing Glutamate Decarboxylase 67 (GAD67). At E14, mouth opening and tongue withdrawal were observed independently at frequency of 14/h each. This movement was rarely observed in the GAD67-deficient mouse. The intraventricular administration of picrotoxin or 3-mercaptopropionic acid abolished mouth opening in the wild-type mice. In a brainstem-spinal cord preparation, three types of neural discharge were recorded: mouth/tongue-moving burst, respiratory burst and irregular activity on the basis of their waveform, regularity in occurrence and concomitant muscle activity. In the GAD67-deficient mice, the occurrence of mouth/tongue-moving burst and irregular activity was inhibited to about 15 and 40% of those in the wild-type mice, respectively. Respiratory burst was slightly inhibited but the difference was not significant. Picrotoxin greatly reduced the frequency of mouth/tongue-moving burst. These results indicate that GABA is involved in rhythm generation in movement of the head region and support the hypothesis that cleft palate in the GAD67-deficient mouse is due to the impairment of mouth or tongue movement that assists palate formation.
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development of spontaneous mouth tongue movement and related neural activity and their repression in fetal mice lacking Glutamate Decarboxylase 67
European Journal of Neuroscience, 2005Co-Authors: Naoko Tsunekawa, Akiko Arata, Kunihiko ObataAbstract:Spontaneous body movement starts at early fetal stage, at embryonic day (E) 12-15 in mice. In the present study, the movement of the head region was studied in E13-14 mice by in utero ultrasound imaging, together with the in vitro recording of underlying neural activities in the hypoglossal nerve and the ventral root of the upper cervical cord of an isolated brainstem-spinal cord preparation. The role of gamma-aminobutyric acid (GABA) in the generation of fetal movement was assessed using mice lacking GABA-synthesizing Glutamate Decarboxylase 67 (GAD67). At E14, mouth opening and tongue withdrawal were observed independently at frequency of 14/h each. This movement was rarely observed in the GAD67-deficient mouse. The intraventricular administration of picrotoxin or 3-mercaptopropionic acid abolished mouth opening in the wild-type mice. In a brainstem-spinal cord preparation, three types of neural discharge were recorded: mouth/tongue-moving burst, respiratory burst and irregular activity on the basis of their waveform, regularity in occurrence and concomitant muscle activity. In the GAD67-deficient mice, the occurrence of mouth/tongue-moving burst and irregular activity was inhibited to about 15 and 40% of those in the wild-type mice, respectively. Respiratory burst was slightly inhibited but the difference was not significant. Picrotoxin greatly reduced the frequency of mouth/tongue-moving burst. These results indicate that GABA is involved in rhythm generation in movement of the head region and support the hypothesis that cleft palate in the GAD67-deficient mouse is due to the impairment of mouth or tongue movement that assists palate formation.
Akiko Arata - One of the best experts on this subject based on the ideXlab platform.
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Development of spontaneous mouth/tongue movement and related neural activity, and their repression in fetal mice lacking Glutamate Decarboxylase 67
The European journal of neuroscience, 2005Co-Authors: Naoko Tsunekawa, Akiko Arata, Kunihiko ObataAbstract:Spontaneous body movement starts at early fetal stage, at embryonic day (E) 12-15 in mice. In the present study, the movement of the head region was studied in E13-14 mice by in utero ultrasound imaging, together with the in vitro recording of underlying neural activities in the hypoglossal nerve and the ventral root of the upper cervical cord of an isolated brainstem-spinal cord preparation. The role of gamma-aminobutyric acid (GABA) in the generation of fetal movement was assessed using mice lacking GABA-synthesizing Glutamate Decarboxylase 67 (GAD67). At E14, mouth opening and tongue withdrawal were observed independently at frequency of 14/h each. This movement was rarely observed in the GAD67-deficient mouse. The intraventricular administration of picrotoxin or 3-mercaptopropionic acid abolished mouth opening in the wild-type mice. In a brainstem-spinal cord preparation, three types of neural discharge were recorded: mouth/tongue-moving burst, respiratory burst and irregular activity on the basis of their waveform, regularity in occurrence and concomitant muscle activity. In the GAD67-deficient mice, the occurrence of mouth/tongue-moving burst and irregular activity was inhibited to about 15 and 40% of those in the wild-type mice, respectively. Respiratory burst was slightly inhibited but the difference was not significant. Picrotoxin greatly reduced the frequency of mouth/tongue-moving burst. These results indicate that GABA is involved in rhythm generation in movement of the head region and support the hypothesis that cleft palate in the GAD67-deficient mouse is due to the impairment of mouth or tongue movement that assists palate formation.
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development of spontaneous mouth tongue movement and related neural activity and their repression in fetal mice lacking Glutamate Decarboxylase 67
European Journal of Neuroscience, 2005Co-Authors: Naoko Tsunekawa, Akiko Arata, Kunihiko ObataAbstract:Spontaneous body movement starts at early fetal stage, at embryonic day (E) 12-15 in mice. In the present study, the movement of the head region was studied in E13-14 mice by in utero ultrasound imaging, together with the in vitro recording of underlying neural activities in the hypoglossal nerve and the ventral root of the upper cervical cord of an isolated brainstem-spinal cord preparation. The role of gamma-aminobutyric acid (GABA) in the generation of fetal movement was assessed using mice lacking GABA-synthesizing Glutamate Decarboxylase 67 (GAD67). At E14, mouth opening and tongue withdrawal were observed independently at frequency of 14/h each. This movement was rarely observed in the GAD67-deficient mouse. The intraventricular administration of picrotoxin or 3-mercaptopropionic acid abolished mouth opening in the wild-type mice. In a brainstem-spinal cord preparation, three types of neural discharge were recorded: mouth/tongue-moving burst, respiratory burst and irregular activity on the basis of their waveform, regularity in occurrence and concomitant muscle activity. In the GAD67-deficient mice, the occurrence of mouth/tongue-moving burst and irregular activity was inhibited to about 15 and 40% of those in the wild-type mice, respectively. Respiratory burst was slightly inhibited but the difference was not significant. Picrotoxin greatly reduced the frequency of mouth/tongue-moving burst. These results indicate that GABA is involved in rhythm generation in movement of the head region and support the hypothesis that cleft palate in the GAD67-deficient mouse is due to the impairment of mouth or tongue movement that assists palate formation.
Martin E. Schwab - One of the best experts on this subject based on the ideXlab platform.
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Characterization of epidermal neural crest stem cell (EPI-NCSC) grafts in the lesioned spinal cord.
Molecular and Cellular Neuroscience, 2006Co-Authors: Maya Sieber-blum, Lisa Schnell, Milos Grim, Regula Schneider, Martin E. SchwabAbstract:Abstract We have characterized in the contusion-lesioned murine spinal cord the behavior of acutely implanted epidermal neural crest stem cells (EPI-NCSC, formerly eNCSC). EPI-NCSC, a novel type of multipotent adult stem cell, are remnants of the embryonic neural crest. They reside in the bulge of hair follicles and have the ability to differentiate into all major neural crest derivatives (Sieber-Blum, M., Grim, M., Hu, Y.F., Szeder, V., 2004. Pluripotent neural crest stem cells in the adult hair follicle. Dev. Dyn. 231, 258–269). Grafted EPI-NCSC survived, integrated, and intermingled with host neurites in the lesioned spinal cord. EPI-NCSC were non-migratory. They did not proliferate and did not form tumors. Significant subsets expressed neuron-specific β-III tubulin, the GABAergic marker Glutamate Decarboxylase 67 (GAD67), the oligodendrocyte marker, RIP, or myelin basic protein (MBP). Close physical association of non-neuronal EPI-NCSC with host neurites was observed. Glial fibrillary acidic protein (GFAP) immunofluorescence was not detected. Collectively, our data indicate that intraspinal EPI-NCSC demonstrate several desirable characteristics that may include local neural replacement and re-myelination.
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Characterization of epidermal neural crest stem cell (EPI-NCSC) grafts in the lesioned spinal cord.
Molecular and cellular neurosciences, 2006Co-Authors: Maya Sieber-blum, Lisa Schnell, Milos Grim, Regula Schneider, Martin E. SchwabAbstract:We have characterized in the contusion-lesioned murine spinal cord the behavior of acutely implanted epidermal neural crest stem cells (EPI-NCSC, formerly eNCSC). EPI-NCSC, a novel type of multipotent adult stem cell, are remnants of the embryonic neural crest. They reside in the bulge of hair follicles and have the ability to differentiate into all major neural crest derivatives (Sieber-Blum, M., Grim, M., Hu, Y.F., Szeder, V., 2004. Pluripotent neural crest stem cells in the adult hair follicle. Dev. Dyn. 231, 258-269). Grafted EPI-NCSC survived, integrated, and intermingled with host neurites in the lesioned spinal cord. EPI-NCSC were non-migratory. They did not proliferate and did not form tumors. Significant subsets expressed neuron-specific beta-III tubulin, the GABAergic marker Glutamate Decarboxylase 67 (GAD67), the oligodendrocyte marker, RIP, or myelin basic protein (MBP). Close physical association of non-neuronal EPI-NCSC with host neurites was observed. Glial fibrillary acidic protein (GFAP) immunofluorescence was not detected. Collectively, our data indicate that intraspinal EPI-NCSC demonstrate several desirable characteristics that may include local neural replacement and re-myelination.