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Publication : Region-specific Expression of NMDA Receptor GluN2C Subunit in Parvalbumin-Positive Neurons and Astrocytes: Analysis of GluN2C Expression using a Novel Reporter Model.

First Author  Ravikrishnan A Year  2018
Journal  Neuroscience Volume  380
Pages  49-62 PubMed ID  29559384
Mgi Jnum  J:262716 Mgi Id  MGI:6162148
Doi  10.1016/j.neuroscience.2018.03.011 Citation  Ravikrishnan A, et al. (2018) Region-specific Expression of NMDA Receptor GluN2C Subunit in Parvalbumin-Positive Neurons and Astrocytes: Analysis of GluN2C Expression using a Novel Reporter Model. Neuroscience 380:49-62
abstractText  Hypofunction of NMDA receptors in parvalbumin (PV)-positive interneurons has been proposed as a potential mechanism for cortical abnormalities and symptoms in schizophrenia. GluN2C-containing receptors have been linked to this hypothesis due to the higher affinity of psychotomimetic doses of ketamine for GluN1/2C receptors. However, the precise cell-type expression of GluN2C subunit remains unknown. We describe the expression of the GluN2C subunit using a novel EGFP reporter model. We observed EGFP(GluN2C) localization in PV-positive neurons in the nucleus reticularis of the thalamus, globus pallidus externa and interna, ventral pallidum and substantia nigra. In contrast, EGFP(GluN2C)-expressing cells did not co-localize with PV-positive neurons in the cortex, striatum, hippocampus or amygdala. Instead, EGFP(GluN2C) expression in these regions co-localized with an astrocytic marker. We confirmed functional expression of GluN2C-containing receptors in the PV-neurons in substantia nigra and cortical astrocytes using electrophysiology. GluN2C was found to be enriched in several first-order and higher order thalamic nuclei. Interestingly, we found that a previous GluN2C beta-gal reporter model excluded expression from PV-neurons and certain thalamic nuclei but exhibited expression in the retrosplenial cortex. GluN2C's unique distribution in neuronal and non-neuronal cells in a brain region-specific manner raises interesting questions regarding the role of GluN2C-containing receptors in the central nervous system.
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