These authors contributed equally to this study.
Mammalian retinal horizontal cells are unconventional GABAergic neurons
Article first published online: 13 DEC 2010
© 2010 The Authors. Journal of Neurochemistry © 2010 International Society for Neurochemistry
Journal of Neurochemistry
Volume 116, Issue 3, pages 350–362, February 2011
How to Cite
Deniz, S., Wersinger, E., Schwab, Y., Mura, C., Erdelyi, F., Szabó, G., Rendon, A., Sahel, J.-A., Picaud, S. and Roux, M. J. (2011), Mammalian retinal horizontal cells are unconventional GABAergic neurons. Journal of Neurochemistry, 116: 350–362. doi: 10.1111/j.1471-4159.2010.07114.x
- Issue published online: 7 JAN 2011
- Article first published online: 13 DEC 2010
- Accepted manuscript online: 19 NOV 2010 10:39AM EST
- Received August 4, 2010; revised manuscript received November 9, 2010; accepted November 10, 2010.
- horizontal cell;
- inhibitory transmission;
- neurotransmitter transporter;
- vesicular release
J. Neurochem. (2011) 116, 350–362.
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.