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GlyT1 determines the glycinergic phenotype of amacrine cells in the mouse retina

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Abstract

The amino acid glycine acts as a neurotransmitter at both inhibitory glycinergic and excitatory glutamatergic synapses predominantly in caudal regions of the central nervous system but also in frontal brain regions and the retina. After its presynaptic release and binding to postsynaptic receptors at caudal glycinergic synapses, two high-affinity glycine transporters GlyT1 and GlyT2 remove glycine from the extracellular space. Glycinergic neurons express GlyT2, which is essential for the presynaptic replenishment of the transmitter, while glial-expressed GlyT1 was shown to control the extracellular glycine concentration. Here we show that GlyT1 expressed by glycinergic amacrine cells of the retina does not only contribute to the control of the extracellular glycine concentration in the retina but is also essential for the maintenance of the glycinergic transmitter phenotype of this cell population. Specifically, loss of GlyT1 from the glycinergic AII amacrine cells impairs AII-mediated glycinergic neurotransmission and alters regulation of the extracellular glycine concentration, without changes in the overall distribution and/or size of glycinergic synapses. Taken together, our results suggest that GlyT1 expressed by amacrine cells in the retina combines functions covered by neuronal GlyT2 and glial GlyT1 at caudal glycinergic synapses.

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Acknowledgements

The authors thank Renate Kühnhauser, Marina Kleber and Freya Boggasch for excellent technical assistance. Parts of this work were supported by Grants from the Deutsche Forschungsgemeinschaft to V. E. (EU110/3-1 and EU110/6-1).

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Author notes

  1. Volker Eulenburg & Katharina Hauf

    Present address: Department of Anesthesiology and Intensive Care Medicine, University of Leipzig, Liebigstrasse 20, 04103, Leipzig, Germany

Authors and Affiliations

  1. Department of Biochemistry and Molecular Medicine, Institute of Biochemistry, Friedrich-Alexander University of Erlangen-Nürnberg, Erlangen, Germany

    Volker Eulenburg, Stefanie Schuster, Katharina Hauf & Julia Schneider

  2. Department of Biology, Animal Physiology, Friedrich-Alexander-University of Erlangen-Nürnberg, Erlangen, Germany

    Gabriel Knop, Tina Sedmak, Andreas Feigenspan, Anneka Joachimsthaler & Johann Helmut Brandstätter

  3. Department of Ophthalmology, University Hospital Erlangen, 91054, Erlangen, Germany

    Anneka Joachimsthaler

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  1. Volker Eulenburg
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Contributions

VE, GK, and JHB designed experiments. GK, TS, SS, KH, JS, AJ, AF, and VE performed experiments. GK, TS, KH, JHB, AF, and VE analyzed data, VE wrote the manuscript with comments from all coauthors. All authors agreed on the final version of the manuscript.

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Correspondence to Volker Eulenburg.

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Eulenburg, V., Knop, G., Sedmak, T. et al. GlyT1 determines the glycinergic phenotype of amacrine cells in the mouse retina. Brain Struct Funct 223, 3251–3266 (2018). https://doi.org/10.1007/s00429-018-1684-3

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  • DOI: https://doi.org/10.1007/s00429-018-1684-3

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