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Lois Miraucourt "Modulation of retinal ganglion cell excitability by chloride pumping: role of extrasynaptic glycine receptors and endocannabinoids."

Abstract :


Type I cannabinoid receptor (CB1R) is present throughout the retina of all vertebrates, from human to fish, however no clear functional role has yet been shown for the endocannabinoid system (ECS) on vision.
Using a behavioral assay based on their innate ability to avoid dark moving dots, we found that Xenopus tadpoles treated with CB1R agonist WIN performed better than control animals under low light conditions. WIN enhanced the tectal neurons EPSCs evoked by electrical stimulation of retinal ganglion cells (RGCs). The CB1R antagonist AM-251, the glycine receptor antagonist strychnine or the NKCC1 chloride transporter blocker bumetanide blocked this effect. Responses evoked by stimulation of the optic tract in an isolated brain preparation were unaffected by bath application of WIN, implicating the retina as the site of relevant CB1R activation. WIN increases the spike frequency of RGCs to visual stimulation, an effect that was also prevented by pretreatment with AM-251, strychnine or bumetanide. However, ERGs, which measure responses in the outer retina, showed no effect of WIN on light-evoked response. To investigate the role of chloride in the excitability change of RGCs we performed 2-photon imaging of retinal neurons expressing the fluorescent chloride indicator clomeleon. WIN rapidly decreased the intracellular chloride concentration of RGCs, but induced no change in bipolar, amacrine or Muller glia cell types. These results present a model where the ECS improves vision at low light conditions by modulation of chloride homeostasis in RGCs to increase excitability.

Selected publications

GABA expression and regulation by sensory experience in the developing visual system. Miraucourt LS, Silva JS, Burgos K, Li J, Abe H, Ruthazer ES, Cline HT.PLoS One. 2012;7(1):e29086. Epub 2012 Jan 5.
Glycine inhibitory dysfunction turns touch into pain through astrocyte-derived D-serine. Miraucourt LS, Peirs C, Dallel R, Voisin DL.Pain. 2011 Jun;152(6):1340-8. Epub 2011 Mar 9.

Glycine inhibitory dysfunction induces a selectively dynamic, morphine-resistant, and neurokinin 1 receptor- independent mechanical allodynia. Miraucourt LS, Moisset X, Dallel R, Voisin DL.J Neurosci. 2009 Feb 25;29(8):2519-27.

Daniel Voisin et Giovanni Marsicano