PMID- 29651654 OWN - NLM STAT- MEDLINE DCOM- 20190314 LR - 20200225 IS - 1573-6903 (Electronic) IS - 0364-3190 (Print) IS - 0364-3190 (Linking) VI - 44 IP - 1 DP - 2019 Jan TI - In the Telencephalon, GluN2C NMDA Receptor Subunit mRNA is Predominately Expressed in Glial Cells and GluN2D mRNA in Interneurons. PG - 61-77 LID - 10.1007/s11064-018-2526-7 [doi] AB - N-methyl-D-aspartate receptors (NMDARs) are widely distributed in the brain with high concentrations in the telencephalon where they modulate synaptic plasticity, working memory, and other functions. While the actions of the predominate GluN2 NMDAR subunits, GluN2A and GluN2B are relatively well understood, the function of GluN2C and GluN2D subunits in the telencephalon is largely unknown. To better understand the possible role of GluN2C subunits, we used fluorescence in situ hybridization (FISH) together with multiple cell markers to define the distribution and type of cells expressing GluN2C mRNA. Using a GluN2C-KO mouse as a negative control, GluN2C mRNA expression was only found in non-neuronal cells (NeuN-negative cells) in the hippocampus, striatum, amygdala, and cerebral cortex. For these regions, a significant fraction of GFAP-positive cells also expressed GluN2C mRNA. Overall, for the telencephalon, the globus pallidus and olfactory bulb were the only regions where GluN2C was expressed in neurons. In contrast to GluN2C, GluN2D subunit mRNA colocalized with neuronal and not astrocyte markers or GluN2C mRNA in the telencephalon (except for the globus pallidus). GluN2C mRNA did, however, colocalize with GluN2D in the thalamus where neuronal GluN2C expression is found. These findings strongly suggest that GluN2C has a very distinct function in the telencephalon compared to its role in other brain regions and compared to other GluN2-containing NMDARs. NMDARs containing GluN2C may have a specific role in regulating L-glutamate or D-serine release from astrocytes in response to L-glutamate spillover from synaptic activity. FAU - Alsaad, Hassan A AU - Alsaad HA AD - Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5800, USA. FAU - DeKorver, Nicholas W AU - DeKorver NW AD - Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5800, USA. FAU - Mao, Zhihao AU - Mao Z AD - Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5800, USA. FAU - Dravid, Shashank M AU - Dravid SM AD - Department of Pharmacology, Creighton University, Omaha, NE, USA. FAU - Arikkath, Jyothi AU - Arikkath J AD - Department of Developmental Neuroscience, Monroe Meyer Institute, University of Nebraska Medical Center, Omaha, NE, USA. FAU - Monaghan, Daniel T AU - Monaghan DT AUID- ORCID: 0000-0002-3261-1901 AD - Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5800, USA. dtmonagh@unmc.edu. LA - eng GR - P30 GM110768/GM/NIGMS NIH HHS/United States GR - MH60252/National Institutes of Health (US)/ GR - R01 MH060252/MH/NIMH NIH HHS/United States GR - GM110768/National Institutes of Health (US)/ GR - R21 NS104705/NS/NINDS NIH HHS/United States PT - Journal Article DEP - 20180412 PL - United States TA - Neurochem Res JT - Neurochemical research JID - 7613461 RN - 0 (NR2C NMDA receptor) RN - 0 (NR2D NMDA receptor) RN - 0 (Protein Subunits) RN - 0 (RNA, Messenger) RN - 0 (Receptors, N-Methyl-D-Aspartate) SB - IM MH - Animals MH - Gene Expression MH - Interneurons/*metabolism MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Neuroglia/*metabolism MH - Protein Subunits/biosynthesis/genetics MH - RNA, Messenger/*biosynthesis/genetics MH - Receptors, N-Methyl-D-Aspartate/*biosynthesis/genetics MH - Telencephalon/*metabolism PMC - PMC6349034 MID - NIHMS979296 OTO - NOTNLM OT - Astrocyte OT - Cortex OT - GluN2C OT - GluN2D OT - Hippocampus OT - L-glutamate OT - N-methyl-D-aspartate receptor OT - mRNA EDAT- 2018/04/14 06:00 MHDA- 2019/03/15 06:00 PMCR- 2020/01/01 CRDT- 2018/04/14 06:00 PHST- 2018/02/13 00:00 [received] PHST- 2018/04/06 00:00 [accepted] PHST- 2018/03/30 00:00 [revised] PHST- 2018/04/14 06:00 [pubmed] PHST- 2019/03/15 06:00 [medline] PHST- 2018/04/14 06:00 [entrez] PHST- 2020/01/01 00:00 [pmc-release] AID - 10.1007/s11064-018-2526-7 [pii] AID - 10.1007/s11064-018-2526-7 [doi] PST - ppublish SO - Neurochem Res. 2019 Jan;44(1):61-77. doi: 10.1007/s11064-018-2526-7. Epub 2018 Apr 12.