Dopamine D1 and D4 receptors contribute to light adaptation in ON-sustained retinal ganglion cells.

The adaptation of ganglion cells to increasing light levels is a crucial property of the retina. The retina must respond to light intensities that vary by 10-12 orders of magnitude, but the dynamic range of ganglion cell responses covers only ∼3 orders of magnitude. Dopamine is a crucial neuromodulator for light adaptation and activates receptors in the D1 and D2 families. Dopamine type D1 receptors (D1Rs) are expressed on horizontal cells and some bipolar, amacrine, and ganglion cells. In the D2 family, D2Rs are expressed on dopaminergic amacrine cells and D4Rs are primarily expressed on photoreceptors. However, the roles of activating these receptors to modulate the synaptic properties of the inputs to ganglion cells are not yet clear. Here, we used single-cell retinal patch-clamp recordings from the mouse retina to determine how activating D1Rs and D4Rs changed the light-evoked and spontaneous excitatory inputs to ON-sustained (ON-s) ganglion cells. We found that both D1R and D4R activation decrease the light-evoked excitatory inputs to ON-s ganglion cells, but that only the sum of the peak response decrease due to activating the two receptors was similar to the effect of light adaptation to a rod-saturating background. The largest effects on spontaneous excitatory activity of both D1R and D4R agonists was on the frequency of events, suggesting that both D1Rs and D4Rs are acting upstream of the ganglion cells. Dopamine by bright light conditions allows retinal neurons to reduce sensitivity to adapt to bright light conditions. It is not clear how and why dopamine receptors modulate retinal ganglion cell signaling. We found that both D1 and D4 dopamine receptors in photoreceptors and inner retinal neurons contribute significantly to the reduction in sensitivity of ganglion cells with light adaptation. However, light adaptation also requires dopamine-independent mechanisms that could reflect inherent sensitivity changes in photoreceptors.