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Glutamate receptors of the delta family are widely expressed in the adult brain

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An Erratum to this article was published on 20 August 2014

Abstract

Recent reports point to critical roles of glutamate receptor subunit delta2 (GluD2) at excitatory synapses and link GluD1 gene alteration to schizophrenia but the expression patterns of these subunits in the brain remain almost uncharacterized. We examined the distribution of GluD1–2 mRNAs and proteins in the adult rodent brain, focusing mainly on GluD1. In situ hybridization revealed widespread neuronal expression of the GluD1 mRNA, with higher levels occurring in several forebrain regions and lower levels in cerebellum. Quantitative RT-PCR assessed differential GluD1 expression in cortex and cerebellum, and revealed GluD2 expression in cortex, albeit at markedly lower level than in cerebellum. Likewise, a high GluD1/GluD2 mRNA ratio was observed in cortex and a low ratio in cerebellum. GluD1 and GluD2 mRNAs were co-expressed in single cortical and hippocampal neurons, with a large predominance of GluD1. Western blots using GluD1- and GluD2-specific antibodies showed expression of both subunits in various brain structures, but not in non-nervous tissues examined. Both delta subunits were upregulated during postnatal development. Widespread neuronal expression of the GluD1 protein was confirmed using immunohistochemistry. Examination at the electron microscopic level in the hippocampus revealed that GluD1 was mainly localized at postsynaptic density of excitatory synapses on pyramidal cells. Control experiments performed using mice carrying deletion of the GluD1- or the GluD2-encoding gene confirmed the specificity of the present mRNA and protein analyses. Our results support a role for the delta family of glutamate receptors at excitatory synapses in neuronal networks throughout the adult brain.

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Acknowledgments

The authors thank Delphine Bouteiller, Thierry Galli, Yannick Marie and Agathe Verraes for their valuable help. We thank Jian Zuo and Carole Levenes for sharing GRID1 KO and GRID2 HO mouse line respectively. S.N. is a fellow of the Nakajima Foundation. This work was supported by grants from Agence Nationale de la Recherche (ANR# BLAN-SVSE4-LS-110624, “IHU Institut de Neurosciences Translationnelles de Paris”; “Investissements d’avenir” ANR-10-IAIHU-06), Fondation pour la Recherche sur le Cerveau/Rotary Club de France, and from the Spanish Ministry of Education and Science (BFU2012-38348 and CONSOLIDER CSD2008-00005) to R.L.

Conflict of interest

The authors declare no competing financial interests.

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Authors and Affiliations

  1. Sorbonne Universités, UPMC Univ Paris 06, UM CR 18, Neuroscience Paris Seine, 75005, Paris, France

    Régine Hepp, Y. Audrey Hay, Shinobu Nomura, Odile Poirel, Salah El Mestikawy, Bertrand Lambolez & Ludovic Tricoire

  2. Centre National de la Recherche Scientifique (CNRS), UMR 8246, Paris, France

    Régine Hepp, Y. Audrey Hay, Shinobu Nomura, Odile Poirel, Salah El Mestikawy, Bertrand Lambolez & Ludovic Tricoire

  3. Institut national de la Santé et de la Recherche Médicale (INSERM), UMR-S 1130, Paris, France

    Régine Hepp, Y. Audrey Hay, Shinobu Nomura, Odile Poirel, Salah El Mestikawy, Bertrand Lambolez & Ludovic Tricoire

  4. Departamento de Ciencias Médicas, Facultad de Medicina, Instituto de Investigación en Discapacidades Neurológicas (IDINE), Universidad Castilla-La Mancha, Campus Biosanitario, C/Almansa 14, 02008, Albacete, Spain

    Carolina Aguado & Rafael Lujan

  5. Sorbonne Universités, UPMC Univ Paris 06, Inserm, CNRS, UM 75, U1127, UMR 7225, ICM, 75013, Paris, France

    Luce Dauphinot & Marie Claude Potier

  6. Department of Psychiatry, Douglas Hospital Research Center, McGill University, Montreal, Quebec, H4H 1R3, Canada

    Salah El Mestikawy

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  1. Régine Hepp
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  2. Y. Audrey Hay
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  3. Carolina Aguado
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  4. Rafael Lujan
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  5. Luce Dauphinot
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  7. Shinobu Nomura
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  9. Salah El Mestikawy
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  10. Bertrand Lambolez
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  11. Ludovic Tricoire
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Correspondence to Ludovic Tricoire.

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B. Lambolez and L. Tricoire contributed equally.

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Hepp, R., Hay, Y.A., Aguado, C. et al. Glutamate receptors of the delta family are widely expressed in the adult brain. Brain Struct Funct 220, 2797–2815 (2015). https://doi.org/10.1007/s00429-014-0827-4

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