An NMDA Receptor-Dependent Mechanism Underlies Inhibitory Synapse Development
In the mammalian brain, GABAergic synaptic transmission provides inhibitory balance to glutamatergic excitatory drive and controls neuronal output. The molecular mechanisms underlying the development of GABAergic synapses remain largely unclear. Here, we report that NMDA-type ionotropic glutamate re...
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doaj-0083f2ffe05c4d8482a43faaa74c3ceb2020-11-25T01:14:57ZengElsevierCell Reports2211-12472016-01-0114347147810.1016/j.celrep.2015.12.061An NMDA Receptor-Dependent Mechanism Underlies Inhibitory Synapse DevelopmentXinglong Gu0Liang Zhou1Wei Lu2Synapse and Neural Circuit Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 35 Convent Drive, 3C1000, Bethesda, MD 20892, USASynapse and Neural Circuit Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 35 Convent Drive, 3C1000, Bethesda, MD 20892, USASynapse and Neural Circuit Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 35 Convent Drive, 3C1000, Bethesda, MD 20892, USAIn the mammalian brain, GABAergic synaptic transmission provides inhibitory balance to glutamatergic excitatory drive and controls neuronal output. The molecular mechanisms underlying the development of GABAergic synapses remain largely unclear. Here, we report that NMDA-type ionotropic glutamate receptors (NMDARs) in individual immature neurons are the upstream signaling molecules essential for GABAergic synapse development, which requires signaling via Calmodulin binding motif in the C0 domain of the NMDAR GluN1 subunit. Interestingly, in neurons lacking NMDARs, whereas GABAergic synaptic transmission is strongly reduced, the tonic inhibition mediated by extrasynaptic GABAA receptors is increased, suggesting a compensatory mechanism for the lack of synaptic inhibition. These results demonstrate a crucial role for NMDARs in specifying the development of inhibitory synapses, and suggest an important mechanism for controlling the establishment of the balance between synaptic excitation and inhibition in the developing brain.http://www.sciencedirect.com/science/article/pii/S2211124715015028 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xinglong Gu Liang Zhou Wei Lu |
spellingShingle |
Xinglong Gu Liang Zhou Wei Lu An NMDA Receptor-Dependent Mechanism Underlies Inhibitory Synapse Development Cell Reports |
author_facet |
Xinglong Gu Liang Zhou Wei Lu |
author_sort |
Xinglong Gu |
title |
An NMDA Receptor-Dependent Mechanism Underlies Inhibitory Synapse Development |
title_short |
An NMDA Receptor-Dependent Mechanism Underlies Inhibitory Synapse Development |
title_full |
An NMDA Receptor-Dependent Mechanism Underlies Inhibitory Synapse Development |
title_fullStr |
An NMDA Receptor-Dependent Mechanism Underlies Inhibitory Synapse Development |
title_full_unstemmed |
An NMDA Receptor-Dependent Mechanism Underlies Inhibitory Synapse Development |
title_sort |
nmda receptor-dependent mechanism underlies inhibitory synapse development |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2016-01-01 |
description |
In the mammalian brain, GABAergic synaptic transmission provides inhibitory balance to glutamatergic excitatory drive and controls neuronal output. The molecular mechanisms underlying the development of GABAergic synapses remain largely unclear. Here, we report that NMDA-type ionotropic glutamate receptors (NMDARs) in individual immature neurons are the upstream signaling molecules essential for GABAergic synapse development, which requires signaling via Calmodulin binding motif in the C0 domain of the NMDAR GluN1 subunit. Interestingly, in neurons lacking NMDARs, whereas GABAergic synaptic transmission is strongly reduced, the tonic inhibition mediated by extrasynaptic GABAA receptors is increased, suggesting a compensatory mechanism for the lack of synaptic inhibition. These results demonstrate a crucial role for NMDARs in specifying the development of inhibitory synapses, and suggest an important mechanism for controlling the establishment of the balance between synaptic excitation and inhibition in the developing brain. |
url |
http://www.sciencedirect.com/science/article/pii/S2211124715015028 |
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