Identification of Amacrine Neurons with a Glycinergic and Gabaergic Phenotype in the Mouse Retina
Main Article Content
Abstract
The amacrine neurons in the mammalian retina comprise a large variety of cell types with distinct properties and functions that serve to integrate and modulate signals presented to output neurons. The majority of them use either glycine or GABA as inhibitory neurotransmitters and express the glycine transporter 1 (GlyT1) or glutamic acid decarboxylase (GAD67) and GABA transporters (GAT1 and GAT3), as a glycinergic or GABAergic marker respectively. We report here a novel subpopulation of amacrine neurons expressing both, GABAergic and glycinergic markers, in retinas from wild-type C57BL/6J mice and two transgenic lines. In retinal sections from the transgenic line expressing eGFP under the control of the glycine transporter 2, eGFP expression was exclusively found in cell bodies and dendrites of inhibitory amacrine neurons, identified for their immunoreactivity to syntaxin 1A. All of the glycinergic and a large portion of the GABAergic amacrine neurons contained eGFP; of these, 8-10% of GlyT1 positive neurons were also labeled either with GAD67, GAT1 or GAT3. These findings were confirmed in retinas from a wild-type and a mouse line expressing eGFP under the GAD67 promoter and two different anti-GlyT1 antibodies, showing the presence of a subpopulation with a dual phenotype. Moreover, eGFP-positive dendrites on both mouse lines were found juxtaposed to GlyR subunits and the scaffold protein gephyrin in several areas of the inner plexiform layer, demonstrating the glycinergic character of these neurons. This dual phenotype was also demonstrated in primary retina cultures, in which isolated neurons were positive for GlyT1 and GAD67 or GAT1/3. Altogether, these data provide compelling evidence of a subpopulation of dual inhibitory, glycinergic/GABAergic amacrine neurons. The co-release of both neurotransmitters may serve to strengthen the inhibition on ganglion cells under synaptic hyperexcitability.
Keywords:
GABA, amacrine neuron, glycinergic, glycine receptor, Glycine Transporter 1
Article Details
How to Cite
PÉREZ-LEÓN, Jorge Alberto et al.
Identification of Amacrine Neurons with a Glycinergic and Gabaergic Phenotype in the Mouse Retina.
Medical Research Archives, [S.l.], v. 10, n. 1, jan. 2022.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/2624>. Date accessed: 21 nov. 2024.
doi: https://doi.org/10.18103/mra.v10i1.2624.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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13. Wassle, H., Koulen, P., Brandstatter, J. H., Fletcher, E. L., and Becker, C. M. (1998) Glycine and GABA receptors in the mammalian retina. Vision Res 38, 1411-1430
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15. Broer, S., and Gether, U. (2012) The solute carrier 6 family of transporters. Br J Pharmacol 167, 256-278
16. Zafra, F., Aragon, C., Olivares, L., Danbolt, N. C., Gimenez, C., and Storm-Mathisen, J. (1995) Glycine transporters are differentially expressed among CNS cells. J Neurosci 15, 3952-3969
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18. Raiteri, L., and Raiteri, M. (2010) Functional 'glial' GLYT1 glycine transporters expressed in neurons. Journal of neurochemistry 114, 647-653
19. Mohler, H., Boison, D., Singer, P., Feldon, J., Pauly-Evers, M., and Yee, B. K. (2011) Glycine transporter 1 as a potential therapeutic target for schizophrenia-related symptoms: evidence from genetically modified mouse models and pharmacological inhibition. Biochem Pharmacol 81, 1065-1077
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21. Heinze, L., Harvey, R. J., Haverkamp, S., and Wassle, H. (2007) Diversity of glycine receptors in the mouse retina: localization of the alpha4 subunit. J Comp Neurol 500, 693-707
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23. Salceda, R. (2006) Pharmacological properties of glycine uptake in the developing rat retina. Neurochem Int 49, 342-346
24. Cherry, T. J., Trimarchi, J. M., Stadler, M. B., and Cepko, C. L. (2009) Development and diversification of retinal amacrine interneurons at single cell resolution. Proc Natl Acad Sci U S A 106, 9495-9500
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26. Aubrey, K. R., and Supplisson, S. (2018) Heterogeneous Signaling at GABA and Glycine Co-releasing Terminals. Frontiers in synaptic neuroscience 10, 40
27. Noh, J., Seal, R. P., Garver, J. A., Edwards, R. H., and Kandler, K. (2010) Glutamate co-release at GABA/glycinergic synapses is crucial for the refinement of an inhibitory map. Nat Neurosci 13, 232-238
28. Haverkamp, S., and Wassle, H. (2004) Characterization of an amacrine cell type of the mammalian retina immunoreactive for vesicular glutamate transporter 3. J Comp Neurol 468, 251-263
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