Mammalian retinal horizontal cells are unconventional GABAergic neurons

Authors

  • Sercan Deniz,

    1. Department of Neurobiology and Genetics, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR_7104, Inserm U 964, Université de Strasbourg, Illkirch, France
    2. Institut de la Vision, INSERM UMR_S968, CNRS UMR_7210, Université Pierre et Marie Curie Paris 06, Paris, France
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    • These authors contributed equally to this study.

  • Eric Wersinger,

    1. Department of Neurobiology and Genetics, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR_7104, Inserm U 964, Université de Strasbourg, Illkirch, France
    2. Institut de la Vision, INSERM UMR_S968, CNRS UMR_7210, Université Pierre et Marie Curie Paris 06, Paris, France
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    • These authors contributed equally to this study.

    • The present address of Eric Wersinger is The Johns Hopkins University School of Medicine, Department of Otolaryngology Head and Neck Surgery, 720 Rutland Ave. Ross 818, Baltimore, MD 21205, USA.

  • Yannick Schwab,

    1. Imaging Center, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR_7104, Inserm U 964, Université de Strasbourg, Illkirch, France
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  • Carole Mura,

    1. Eurexpress Platform, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR_7104, Inserm U 964, Université de Strasbourg, Illkirch, France
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  • Ferenc Erdelyi,

    1. Department of Gene Technology and Developmental Neurobiology, Institute of Experimental Medicine, Budapest, Hungary
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  • Gábor Szabó,

    1. Eurexpress Platform, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR_7104, Inserm U 964, Université de Strasbourg, Illkirch, France
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  • Alvaro Rendon,

    1. Institut de la Vision, INSERM UMR_S968, CNRS UMR_7210, Université Pierre et Marie Curie Paris 06, Paris, France
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  • José-Alain Sahel,

    1. Institut de la Vision, INSERM UMR_S968, CNRS UMR_7210, Université Pierre et Marie Curie Paris 06, Paris, France
    2. Centre d’Investigation Clinique 503, Inserm-Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts, Paris, France
    3. Fondation Ophtalmologique Adolphe de Rothschild, Paris, France
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  • Serge Picaud,

    1. Institut de la Vision, INSERM UMR_S968, CNRS UMR_7210, Université Pierre et Marie Curie Paris 06, Paris, France
    2. Fondation Ophtalmologique Adolphe de Rothschild, Paris, France
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  • Michel J. Roux

    1. Department of Neurobiology and Genetics, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR_7104, Inserm U 964, Université de Strasbourg, Illkirch, France
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Address correspondence and reprint requests to Michel J. Roux, Department of Neurobiology and Genetics, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR 7104, Inserm U 964, Université de Strasbourg, 1 rue Laurent Fries BP10142, 67404 Illkirch Cedex, France. E-mail: mjroux@igbmc.fr

Abstract

J. Neurochem. (2011) 116, 350–362.

Abstract

Lateral interactions at the first retinal synapse have been initially proposed to involve GABA by transporter-mediated release from horizontal cells, onto GABAA receptors expressed on cone photoreceptor terminals and/or bipolar cell dendrites. However, in the mammalian retina, horizontal cells do not seem to contain GABA systematically or to express membrane GABA transporters. We here report that mouse retinal horizontal cells express GAD65 and/or GAD67 mRNA, and were weakly but consistently immunostained for GAD65/67. While GABA was readily detected after intracardiac perfusion, it was lost during classical preparation for histology or electrophysiology. It could not be restored by incubation in a GABA-containing medium, confirming the absence of membrane GABA transporters in these cells. However, GABA was synthesized de novo from glutamate or glutamine, upon addition of pyridoxal 5′-phosphate, a cofactor of GAD65/67. Mouse horizontal cells are thus atypical GABAergic neurons, with no functional GABA uptake, but a glutamate and/or glutamine transport system allowing GABA synthesis, probably depending physiologically from glutamate released by photoreceptors. Our results suggest that the role of GABA in lateral inhibition may have been underestimated, at least in mammals, and that tissue pre-incubation with glutamine and pyridoxal 5′-phosphate should yield a more precise estimate of outer retinal processing.

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