GABA Expression Dominates Neuronal Lineage Progression in the Embryonic Rat Neocortex and Facilitates Neurite Outgrowth via GABA<sub>A</sub>Autoreceptor/Cl<sup>−</sup>Channels

Maric, Dragan; Liu, Qi‐Ying; Marić, Irina; Chaudry, Sabeen; Chang, Yoong-Hee; Smith, Susan V.; Sieghart, Werner; Fritschy, Jean‐Marc; Barker, Jeffery L.

doi:10.1523/jneurosci.21-07-02343.2001

Cited by 140 publications

(118 citation statements)

References 58 publications

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“…Along with changes in the level of expression, we showed that GABA A R activation in precursors and neuroblasts leads to different physiological outcomes, that is, in neuroblasts it induces depolarization and a rise in Ca 2þ levels, whereas in precursors it is hyperpolarizing and does not increase [Ca 2þ ] i , suggesting that the Cl À gradient is different in these two cell types [35]. This result further highlights the similarity between neonatal SEZ precursors and the embryonic neocortex, where the depolarizing effect of GABA along with increase in [Ca 2þ ] i are primarily confined to cells undergoing neuronal differentiation [36]. Consistent with the opposite effects on membrane potential in the two cell types, osmotic swelling was not observed in neuroblasts but only in precursors, and in particular, in cells expressing prominin.…”

Section: Discussionmentioning

confidence: 76%

GABAA Receptor Signaling Induces Osmotic Swelling and Cell Cycle Activation of Neonatal Prominin+ Precursors

et al. 2011

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Signal-regulated changes in cell size affect cell division and survival and therefore are central to tissue morphogenesis and homeostasis. In this respect, GABA receptors (GABA A Rs) are of particular interest because allowing anions flow across the cell membrane modulates the osmolyte flux and the cell volume. Therefore, we have here investigated the hypothesis that GABA may regulate neural stem cell proliferation by inducing cell size changes. We found that, besides neuroblasts, also neural precursors in the neonatal murine subependymal zone sense GABA via GABA A Rs. However, unlike in neuroblasts, where it induced depolarization-mediated [Ca 21 ] i increase, GABA A Rs activation in precursors caused hyperpolarization. This resulted in osmotic swelling and increased surface expression of epidermal growth factor receptors (EGFRs). Furthermore, activation of GABA A Rs signaling in vitro in the presence of EGF modified the expression of the cell cycle regulators, phosphatase and tensin homolog and cyclin D1, increasing the pool of cycling precursors without modifying cell cycle length. A similar effect was observed on treatment with diazepam. We also demonstrate that GABA and diazepam responsive precursors represent prominin 1 stem cells. Finally, we show that as in in vitro also in in vivo a short administration of diazepam promotes EGFR expression in prominin 1 stem cells causing activation and cell cycle entry. Thus, our data indicate that endogenous GABA is a part of a regulatory mechanism of size and cell cycle entry of neonatal stem cells. Our results also have potential implications for the therapeutic practices that involve exposure to GABA A Rs modulators during neurodevelopment. STEM CELLS 2011;29:307-319 Disclosure of potential conflicts of interest is found at the end of this article.

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Section: Discussionmentioning

confidence: 76%

GABAA Receptor Signaling Induces Osmotic Swelling and Cell Cycle Activation of Neonatal Prominin+ Precursors

et al. 2011

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“…Another possibility, however, is that GABA A receptors serve a trophic role in the growth cone and young synapse, sensing ambient GABA, which could enhance axonal outgrowth. Such a model has been proposed for somatodendritic GABA A receptors in migrating neurons (36,37). Here, GABA A receptor activation leads to weak depolarization and calcium influx through voltage-dependent Ca channels.…”

Section: Discussionmentioning

confidence: 99%

Reciprocal developmental regulation of presynaptic ionotropic receptors

Tureček

Trussell

2002

Proc. Natl. Acad. Sci. U.S.A.

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Activation of ionotropic glycine receptors potentiates glutamate release in mature calyceal nerve terminals of the rat medial nucleus of the trapezoid body, an auditory brainstem nucleus. In young rats, glycine and its receptors are poorly expressed. We therefore asked whether GABA (␥-aminobutyric acid) might play a larger role than glycine in the regulation of glutamate release in the absence of glycine receptors. Indeed, in rats younger than postnatal day 11 (P11), and before the onset of hearing, calyces expressed high levels of ionotropic GABAA receptors but few glycine receptors. Isoguvacine, a selective agonist at GABAA receptors, strongly enhanced excitatory postsynaptic currents in young rats but had little effect in rats older than P11. Down-regulation of presynaptic GABAA receptors did not reflect global changes in receptor expression, because the magnitude of GABA and glycine responses was similar at P13 in the parent-cell bodies of the calyces, the bushy cells of the cochlear nucleus. In outside-out patches excised from the nonsynaptic face of calyces, GABA and glycine evoked singlechannel currents consistent with the properties of postsynaptic GABAA and glycine receptors. Inhibitory GABAB receptors were present on the calyx at all developmental stages examined. Thus, GABA initially acts on two receptor subtypes, both promoting and inhibiting glutamate release. With age, the former role is transferred to the glycine receptor during the period in which postsynaptic glycinergic transmission is acquired. L igand-gated ion channels (ionotropic receptors) aggregate in subsynaptic membrane shortly after pre-and postsynaptic cells come in close contact (1-4). During maturation of the synapse, changes often occur in the subtypes of postsynaptic receptor (5, 6). Recently, it has become clear that many synapses contain presynaptic ionotropic receptors, such as glutamate, GABA A (␥-aminobutyric acid type A), or acetylcholine receptors, whose activation regulates transmitter release in response to presynaptic action potentials (7). Unlike many postsynaptic receptors, it is not known whether presynaptic receptors are expressed in parallel with the development of their corresponding transmitter systems. This problem is accentuated by the fact that presynaptic receptors generally are not directly apposed to presynaptic terminals (axo-axonic synapses) but, rather, are activated by ''spillover'' of transmitter from distant terminals (8, 9). Moreover, it is not known whether these receptors are selectively targeted to axon terminals or, instead, appear in proportion to global changes in receptor expression over the entire neuron.The calyx of Held is a large glutamatergic nerve terminal found on neurons of the medial nucleus of the trapezoid body (MNTB), a brainstem auditory relay nucleus. Postsynaptic neurons in MNTB are glycinergic and supply fast inhibition to diverse targets in the superior olivary complex. We previously have shown that presynaptic glycine receptors are expressed on the calyx terminal and that acti...

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“…In support of this theory, GABA A receptor antagonists (e.g. bicuculline) or agents that block GABA synthesis inhibit neuritic arborization of cortical neurons (Ben-Ari et al, 1994;Maric et al, 2001). Thus, a deficiency in GABA A receptors may perturb the maturation of the inhibitory neural network, in spite of elevated GABA levels that encourage axonal and dendritic development.…”

Section: Gabaergic Protein Expression and Neuronal Development In Thementioning

confidence: 98%

“…Chronic GABA A receptor activation in early development is necessary for the switch from GABA excitation to inhibition in the brain (Ganguly et al, 2001) and in the retina (Leitch et al, 2005). Furthermore, GABA itself promotes neurite length and branching in inhibitory and excitatory cortical neurons from neonatal rats and embryonic chicks (Baloyannis et al, 1983;Spoerri, 1988;Maric et al, 2001). In Fmr1 knockout mice, the dysregulation of GABA A receptor and GABAergic enzyme expression may affect GABA-mediated activity during the critical period.…”

Section: Gabaergic Protein Expression and Neuronal Development In Thementioning

confidence: 99%

Early developmental alterations in GABAergic protein expression in fragile X knockout mice

et al. 2010

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The purpose of this study was to examine the expression of GABAergic proteins in Fmr1 knockout mice during brain maturation and to assess behavioural changes potentially linked to perturbations in the GABAergic system. Quantitative western blotting of the forebrain revealed that compared to wild-type mice, the GABA A receptor α1, β2, and δ subunits, and the GABA catabolic enzymes GABA transaminase and SSADH were down-regulated during postnatal development, while GAD65 was up-regulated in the adult knockout mouse forebrain. In tests of locomotor activity, the suppressive effect on motor activity of the GABA A β2/3 subunit-selective drug loreclezole was impaired in the mutant mice. In addition, sleep time induced by the GABA A β2/3-selective anaesthetic drug etomidate was decreased in the knockout mice. Our results indicate that disruptions in the GABAergic system in the developing brain may result in behavioural consequences in adults with fragile X syndrome.iii

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GABA Expression Dominates Neuronal Lineage Progression in the Embryonic Rat Neocortex and Facilitates Neurite Outgrowth via GABA_AAutoreceptor/Cl⁻Channels

Cited by 140 publications

References 58 publications

GABAA Receptor Signaling Induces Osmotic Swelling and Cell Cycle Activation of Neonatal Prominin+ Precursors

GABAA Receptor Signaling Induces Osmotic Swelling and Cell Cycle Activation of Neonatal Prominin+ Precursors

Reciprocal developmental regulation of presynaptic ionotropic receptors

Early developmental alterations in GABAergic protein expression in fragile X knockout mice

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GABA Expression Dominates Neuronal Lineage Progression in the Embryonic Rat Neocortex and Facilitates Neurite Outgrowth via GABAAAutoreceptor/Cl−Channels

Cited by 140 publications

References 58 publications

GABAA Receptor Signaling Induces Osmotic Swelling and Cell Cycle Activation of Neonatal Prominin+ Precursors

GABAA Receptor Signaling Induces Osmotic Swelling and Cell Cycle Activation of Neonatal Prominin+ Precursors

Reciprocal developmental regulation of presynaptic ionotropic receptors

Early developmental alterations in GABAergic protein expression in fragile X knockout mice

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GABA Expression Dominates Neuronal Lineage Progression in the Embryonic Rat Neocortex and Facilitates Neurite Outgrowth via GABA_AAutoreceptor/Cl⁻Channels