April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Light/Dark Adaptive Regulation of GABAA Receptor and Chloride Cotransporter Expression and Activity Modulates the ON-Pathway Surround
Author Affiliations & Notes
  • Y. Cao
    Dept Neurosci, Ohio State Univ, Columbus, Ohio
  • C. Ribelayga
    Dept Neurosci, Ohio State Univ, Columbus, Ohio
  • S. C. Mangel
    Dept Neurosci, Ohio State Univ, Columbus, Ohio
  • Footnotes
    Commercial Relationships  Y. Cao, None; C. Ribelayga, None; S.C. Mangel, None.
  • Footnotes
    Support  NEI grant EY014235 to S.C.M.
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 3289. doi:
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      Y. Cao, C. Ribelayga, S. C. Mangel; Light/Dark Adaptive Regulation of GABAA Receptor and Chloride Cotransporter Expression and Activity Modulates the ON-Pathway Surround. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3289.

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Abstract

Purpose: : Ganglion cells (GCs) display a center-surround receptive field (RF) following prolonged (>30 min) light adaptation, but lose their surround responses following prolonged dark adaptation (Barlow et al., 1957). Under light-adapted conditions, horizontal cells (HCs) contribute to ON-GC surround responses (Mangel, 1991) possibly by releasing GABA onto ON-bipolar cell (BC) dendrites, which express Cl-permeable GABAA receptor (GABAAR) channels and the Cl cotransporter NKCC. We thus tested whether light/dark adaptive regulation of GABAARs and NKCC mediates light/dark adaptive modulation of the ON-pathway surround.

Methods: : Pigmented rabbits were bright light (photopic)- or dark (low scotopic)-adapted for 1 h or rabbit retinas were incubated in Ringer for 1 h under light-adapted conditions with or without test drugs. Retinal sections were processed in an identical manner for immunostaining with specific antibodies against the β2/3 subunit-containing, GABAAR (MAB341, Millipore) and NKCC (T4, DSHB). Following prolonged light adaptation, the effects of current injections into rabbit HCs on the activity of nearby ON-GCs were studied.

Results: : Intense GABAAR and NKCC antibody labeling were observed in ON-BC dendrites and HC somata under light-adapted control conditions, but both immunosignals were minimal in dark-adapted retinas or in light-adapted retinas pre-treated with the dopamine D1 antagonist SCH23390 or the nitric oxide (NO) synthase inhibitor L-NAME. Under light-adapted conditions, picrotoxin, a GABAA/C antagonist, and bumetanide, a specific NKCC inhibitor, blocked the effect of HC polarizations on ON-GC spike activity. Picrotoxin also eliminated the reduction in the ON-GC center response produced by hyperpolarizing nearby HCs.

Conclusions: : These results suggest that prolonged light adaptation increases D1 receptor activation and NO synthesis so that GABAAR and NKCC expression and activity on the dendrites of ON-BCs are enhanced, producing the RF surrounds of ON-BCs (and ON-GCs). In contrast, following prolonged dark adaptation D1 receptor activation and NO synthesis are minimal so that GABAAR and NKCC expression and activity are substantially reduced, eliminating the RF surrounds of ON-BCs (and ON-GCs).

Keywords: receptive fields • inhibitory receptors • ion transporters 
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