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Eur J Neurosci. 2015 Sep;42(6):2258-70. doi: 10.1111/ejn.12993. Epub 2015 Jul 22.

Dopamine modulation of rod pathway signaling by suppression of GABAC feedback to rod-driven depolarizing bipolar cells.

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Department of Biology, Life Science Centre, Dalhousie University, Halifax, NS, Canada.
Department of Ophthalmology and Visual Sciences, Dalhousie University, Halifax, NS, Canada.
Department of Physiology and Biophysics, Dalhousie University, Halifax, NS, Canada.
IWK Health Centre, Eye Care Team, 5850 University Ave, PO Box 9700, Halifax, NS, Canada, B3K 6R8.


Reducing signal gain in the highly sensitive rod pathway prevents saturation as background light levels increase, allowing the dark-adapted retina to encode stimuli over a range of background luminances. Dopamine release is increased during light adaptation and is generally accepted to suppress rod signaling in light-adapted retinas. However, recent research has suggested that dopamine, acting through D1 receptors, could additionally produce a sensitization of the rod pathway in dim light conditions via gamma-aminobutyric acid (GABA) type C receptors. Here, we evaluated the overall activity of the depolarizing bipolar cell (DBC) population in vivo to ensure the integrity of long-distance network interactions by quantifying the b-wave of the electroretinogram in mice. We showed that dopamine, acting through D1 receptors, reduced the amplitude and sensitivity of rod-driven DBCs during light adaptation by suppressing GABA type A receptor-mediated serial inhibition onto rod DBC GABA type C receptors. Block of D1 receptors did not suppress rod-driven DBC sensitivity when GABAA -mediated serial inhibition was blocked by gabazine, suggesting that the reduction in rod-driven DBC sensitivity in the absence of D1 receptors was due to disinhibition of serial inhibitory GABAergic circuitry rather than a direct facilitatory effect on GABA release onto rod-driven DBC GABA type C receptors. Finally, the large population of GABAergic A17 wide-field amacrine cells known to maintain reciprocal inhibition with rod DBCs could be excluded from the proposed disinhibitory circuit after treatment with 5,7-dihydroxytryptamine.


adaptation; dopamine; gamma-aminobutyric acid; mouse; retina; vision

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