title: GluN2B-containing NMDA receptors promote glutamate synapse development in hippocampal interneurons.
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.
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany.
authors.forename: Wolfgang
authors.identifier: http://orcid.org/0000-0002-3470-8125
authors.initials: W
authors.lastname: Kelsch
authors.affiliation: Department of Clinical Neurobiology, Medical Faculty of Heidelberg University and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Li
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wieland
authors.affiliation: 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.
authors.forename: Oleg
authors.initials: O
authors.lastname: Senkov
authors.affiliation: Department of Clinical Neurobiology, Medical Faculty of Heidelberg University and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Herb
authors.affiliation: 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.
authors.forename: Christina
authors.initials: C
authors.lastname: Göngrich
authors.affiliation: Department of Clinical Neurobiology, Medical Faculty of Heidelberg University and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany, h.monyer@dkfz-heidelberg.de.
authors.forename: Hannah
authors.initials: H
authors.lastname: Monyer
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D005260:Female; D055879:Gene Knock-In Techniques; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000254:growth & development* / Q000378:metabolism*; D007395:Interneurons / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D016194:Receptors, N-Methyl-D-Aspartate / Q000172:deficiency* / Q000502:physiology; D013569:Synapses / Q000378:metabolism*
chemical_list: C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid
keywords: GluN2B; NMDARs; hippocampus; interneurons; postnatal development; seizures