Region-specific Expression of NMDA Receptor GluN2C Subunit in Parvalbumin-Positive Neurons and Astrocytes: Analysis of GluN2C Expression using a Novel Reporter Model.
Region-specific Expression of NMDA Receptor GluN2C Subunit in Parvalbumin-Positive Neurons and Astrocytes: Analysis of GluN2C Expression using a Novel Reporter Model.
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DOI：
10.1016/j.neuroscience.2018.03.011
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发表时间：
2018-06-01
期刊：
影响因子：
3.3
通讯作者：
Dravid SM
中科院分区：
文献类型：
--
作者：
Ravikrishnan A;Gandhi PJ;Shelkar GP;Liu J;Pavuluri R;Dravid SM
小白蛋白(PV)阳性中间神经元上NMDA受体功能低下被认为是精神分裂症患者皮质异常和症状的潜在机制。由于拟精神病剂量的氯胺酮对GluN1/2C受体有较高的亲和力，含有GluN2C的受体与这一假说有关。然而，GluN2C亚基的确切细胞类型表达仍不清楚。我们使用一个新的EGFP报告模型描述了GluN2C亚基的表达。我们观察了绿色荧光蛋白(GluN2C)阳性神经元在丘脑网状核、苍白球外侧部和内侧部、腹侧苍白球和黑质的分布。相反，表达绿色荧光蛋白(GluN2C)的细胞不与皮质区、纹状体、海马区或杏仁核中的PV阳性神经元共存。相反，绿色荧光蛋白(GluN2C)在这些区域的表达与星形细胞标志物共定位。我们用电生理学方法证实了黑质和皮质星形胶质细胞的PV神经元中含有GluN2C受体的功能表达。GluN2C在几个一阶和更高阶丘脑核团中均有丰富。有趣的是，我们发现以前的GluN2Cβ-GAL报告模型排除了PV神经元和某些丘脑核团的表达，但在脾后皮质显示了表达。GluN2C以脑区特异性方式在神经细胞和非神经细胞中的独特分布引发了关于包含GluN2C的受体在中枢神经系统中的作用的有趣的问题。
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 β-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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