June 2015
Volume 56, Issue 7
ARVO Annual Meeting Abstract  |   June 2015
Mechanisms underlying the tonic nature of ipRGCs’ rod/cone-driven photoresponses
Author Affiliations & Notes
  • Xiwu Zhao
    Department of Ophthalmology & Visual Sciences, University of Michigan, Ann Arbor, MI
  • Kwoon Y Wong
    Department of Ophthalmology & Visual Sciences, University of Michigan, Ann Arbor, MI
  • Footnotes
    Commercial Relationships Xiwu Zhao, None; Kwoon Wong, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 5568. doi:
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      Xiwu Zhao, Kwoon Y Wong; Mechanisms underlying the tonic nature of ipRGCs’ rod/cone-driven photoresponses. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5568.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: We showed previously that the rod/cone-driven light responses of ipRGCs are very tonic whereas those of all other RGCs are far more transient. Here, we explored several mechanisms that could account for such kinetics difference.

Methods: This study used three mouse lines in which GFP labeled specific RGC types: the opn4Cre/+;GFP line labeling ipRGCs (Ecker et al. Neuron 2010), the TRHR-GFP line labeling a type of ON-OFF direction-selective RGC (Rivlin-Etzion et al. J. Neurosci. 2011), and the Hoxd10-GFP line labeling ON and ON-OFF RGCs that innervate the accessory optic system (Dhande et al. J. Neurosci. 2013). Dark-adapted retinas were superfused with Ames’ medium. GFP+ cells were targeted using a multiphoton laser for whole-cell recording. All stimuli were receptive field center-selective white spots 200 µm in diameter and 10 sec in duration, with intensities too low to activate melanopsin.

Results: In darkness, prolonged depolarizing current injection induced equally sustained depolarization and spiking in all cell types, whereas bath application of the group III metabotropic glutamate receptor (mGluR) antagonist CPPG depolarized ipRGCs substantially more than the other RGCs. In response to the light spots, ipRGCs depolarized throughout the 10 sec whereas TRHR and Hoxd10 cells seldom depolarized for more than several seconds. The mGluR7 antagonist MMPIP made the photoresponses of ipRGCs and ON Hoxd10 cells more transient but did not affect TRHR or ON-OFF Hoxd10 cells. GABA and glycine receptor antagonists enabled TRHR and Hoxd10 cells to depolarize for the duration of the 10-sec light but only slightly enhanced ipRGC photoresponses. When RGCs were voltage-clamped at ECl to isolate bipolar-driven light responses, the GABA/glycine antagonists dramatically prolonged ON-OFF Hoxd10 cells’ light-evoked currents but affected the other cells minimally. Adding AMPA/kainate desensitization inhibitors on top of the GABA/glycine antagonists had no effect on any of the cells tested.

Conclusions: The CPPG result suggests that ipRGCs are postsynaptic from sustained bipolar cells whereas TRHR and Hoxd10 cells get input from transient bipolars (Awatramani & Slaughter J. Neurosci. 2000). mGluR7 signaling and the relative lack of amacrine-driven inhibition enhance the sustainedness of ipRGC photoresponses. By contrast, AMPA/kainate receptor desensization and intrinsic membrane properties do not shape photoresponse kinetics.


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