title: Dopamine modulation of rod pathway signaling by suppression of GABAC feedback to rod-driven depolarizing bipolar cells.
abstract: 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.
authors.affiliation: Department of Biology, Life Science Centre, Dalhousie University, Halifax, NS, Canada.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Smith
authors.affiliation: Department of Biology, Life Science Centre, Dalhousie University, Halifax, NS, Canada.|Department of Ophthalmology and Visual Sciences, Dalhousie University, Halifax, NS, Canada.
authors.forename: Patrice D
authors.initials: PD
authors.lastname: Côté
authors.affiliation: 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.
authors.forename: François
authors.initials: F
authors.lastname: Tremblay
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000222:Adaptation, Physiological; D025042:Amacrine Cells / Q000502:physiology; D000818:Animals; D003623:Dark Adaptation; D018491:Dopamine Agonists / Q000494:pharmacology; D004596:Electroretinography; D025461:Feedback, Physiological; D051379:Mice; D008810:Mice, Inbred C57BL; D009433:Neural Inhibition; D010721:Phosphinic Acids / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000502:physiology*; D018079:Receptors, GABA / Q000502:physiology*; D051245:Retinal Bipolar Cells / Q000502:physiology*; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology*; D015398:Signal Transduction; D014795:Visual Pathways / Q000502:physiology
chemical_list: C101879:(1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid; D018491:Dopamine Agonists; C087200:GABA-C receptor; D010721:Phosphinic Acids; D011725:Pyridines; D017447:Receptors, Dopamine D1; D018079:Receptors, GABA; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
keywords: adaptation; dopamine; gamma-aminobutyric acid; mouse; retina; vision