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J Neurosci. 2014 Nov 26;34(48):16022-30. doi: 10.1523/JNEUROSCI.1210-14.2014.

GluN2B-containing NMDA receptors promote glutamate synapse development in hippocampal interneurons.

Author information

1
Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany.
2
Department of Clinical Neurobiology, Medical Faculty of Heidelberg University and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
3
Department of Clinical Neurobiology, Medical Faculty of Heidelberg University and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany, Molecular Neuroplasticity Group, DZNE, 39120 Magdeburg, Germany, and.
4
Department of Clinical Neurobiology, Medical Faculty of Heidelberg University and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany, Department of Neuroscience, Karolinska Institute, 171 77 Stockholm, Sweden.
5
Department of Clinical Neurobiology, Medical Faculty of Heidelberg University and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany, h.monyer@dkfz-heidelberg.de.

Abstract

In postnatal development, GluN2B-containing NMDARs are critical for the functional maturation of glutamatergic synapses. GluN2B-containing NMDARs prevail until the second postnatal week when GluN2A subunits are progressively added, conferring mature properties to NMDARs. In cortical principal neurons, deletion of GluN2B results in an increase in functional AMPAR synapses, suggesting that GluN2B-containing NMDARs set a brake on glutamate synapse maturation. The function of GluN2B in the maturation of glutamatergic inputs to cortical interneurons is not known. To examine the function of GluN2B in interneurons, we generated mutant mice with conditional deletion of GluN2B in interneurons (GluN2B(ΔGAD67)). In GluN2B(ΔGAD67) mice interneurons distributed normally in cortical brain regions. After the second postnatal week, GluN2B(ΔGAD67) mice developed hippocampal seizures and died shortly thereafter. Before the onset of seizures, GluN2B-deficient hippocampal interneurons received fewer glutamatergic synaptic inputs than littermate controls, indicating that GluN2B-containing NMDARs positively regulate the maturation of glutamatergic input synapses in interneurons. These findings suggest that GluN2B-containing NMDARs keep the circuit activity under control by promoting the maturation of excitatory synapses in interneurons.

KEYWORDS:

GluN2B; NMDARs; hippocampus; interneurons; postnatal development; seizures

PMID:
25429143
DOI:
10.1523/JNEUROSCI.1210-14.2014
[Indexed for MEDLINE]
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