γ-Aminobutyric acid (GABA): a fast excitatory transmitter which may regulate the development of hippocampal neurones in early postnatal life

Ben-Ari, Yehezkel; Tseeb, Vadim; Raggozzino, D; Khazipov, Roustem; Gaı̈arsa, Jean-Luc

doi:10.1016/s0079-6123(08)60545-2

Cited by 158 publications

(110 citation statements)

References 55 publications

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“…3A-C). These results demonstrated that GABA A receptor-mediated activity increases the frequency of intrinsic CA1 oscillations in excitatory V m depolarization, although GABA A receptors primarily mediate inhibitory synaptic responses in the rat hippocampus after the end of the first postnatal week, the age of animals used in this study [27,28].…”

Section: Intrinsically Generated Oscillatory Membrane Potential Depolmentioning

confidence: 57%

GABAergic Interneurons are Required for Generation of Slow CA1 Oscillation in Rat Hippocampus

Wang

Liu

et al. 2016

Neurosci. Bull.

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Neuronal oscillations are fundamental to hippocampal function. It has been shown that GABAergic interneurons make an important contribution to hippocampal oscillations, but the underlying mechanism is not well understood. Here, using whole-cell recording in the complete hippocampal formation isolated from rats at postnatal days 14-18, we showed that GABA A receptormediated activity enhanced the generation of slow CA1 oscillations. In vitro, slow oscillations (0.5-1.5 Hz) were generated in CA1 neurons, and they consisted primarily of excitatory rather than inhibitory membrane-potential changes. These oscillations were greatly reduced by blocking GABA A receptor-mediated activity with bicuculline and were enhanced by increasing such activity with midazolam, suggesting that interneurons are required for oscillation generation. Consistently, CA1 fast-spiking interneurons were found to generate action potentials usually preceding those in CA1 pyramidal cells. These findings indicate a GABA A receptor-based mechanism for the generation of the slow CA1 oscillation in the hippocampus.

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Section: Intrinsically Generated Oscillatory Membrane Potential Depolmentioning

confidence: 57%

GABAergic Interneurons are Required for Generation of Slow CA1 Oscillation in Rat Hippocampus

Wang

Liu

et al. 2016

Neurosci. Bull.

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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%

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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“…Atypical GABRP can assemble with these known GABA A receptor subunits and the presence of this subunit may alter the sensitivity of GABA A receptors to GABA or modulator agents (5). Although GABA primarily functions as an inhibitory neurotransmitter in the mature CNS, it can also act as a trophic factor during CNS development to modulate the proliferation, migration, and differentiation of neuronal cells (6)(7)(8). GABA and GABA A receptors are also present and function in peripheral tissues other than the CNS, but their precise function in nonneuronal cells, including cancerous cells, is poorly defined at present.…”

Section: Introductionmentioning

confidence: 99%

γ-Aminobutyric Acid (GABA) Stimulates Pancreatic Cancer Growth through Overexpressing GABAA Receptor π Subunit

et al. 2007

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Abstract;-Aminobutyric acid (GABA) functions primarily as an inhibitory neurotransmitter in the mature central nervous system, and GABA/GABA receptors are also present in nonneural tissues, including cancer, but their precise function in nonneuronal or cancerous cells has thus far been poorly defined. Through the genome-wide cDNA microarray analysis of pancreatic ductal adenocarcinoma (PDAC) cells as well as subsequent reverse transcription-PCR and Northern blot analyses, we identified the overexpression of GABA receptor P subunit (GABRP) in PDAC cells. We also found the expression of this peripheral type GABA A receptor subunit in few adult human organs. Knockdown of endogenous GABRP expression in PDAC cells by small interfering RNA attenuated PDAC cell growth, suggesting its essential role in PDAC cell viability. Notably, the addition of GABA into the cell culture medium promoted the proliferation of GABRP-expressing PDAC cells, but not GABRP-negative cells, and GABA A receptor antagonists inhibited this growth-promoting effect by GABA. The HEK293 cells constitutively expressing exogenous GABRP revealed the growth-promoting effect of GABA treatment. Furthermore, GABA treatment in GABRP-positive cells increased intracellular Ca 2+ levels and activated the mitogenactivated protein kinase/extracellular signal-regulated kinase (MAPK/Erk) cascade. Clinical PDAC tissues contained a higher level of GABA than normal pancreas tissues due to the upregulation of glutamate decarboxylase 1 expression, suggesting their autocrine/paracrine growth-promoting effect in PDACs. These findings imply that GABA and GABRP could play important roles in PDAC development and progression, and that this pathway can be a promising molecular target for the development of new therapeutic strategies for PDAC.

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γ-Aminobutyric acid (GABA): a fast excitatory transmitter which may regulate the development of hippocampal neurones in early postnatal life

Cited by 158 publications

References 55 publications

GABAergic Interneurons are Required for Generation of Slow CA1 Oscillation in Rat Hippocampus

GABAergic Interneurons are Required for Generation of Slow CA1 Oscillation in Rat Hippocampus

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

γ-Aminobutyric Acid (GABA) Stimulates Pancreatic Cancer Growth through Overexpressing GABAA Receptor π Subunit

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