Abstract
Dopamine is a key neurotransmitter in the retina and plays a central role in the light adaptive processes of the visual system. The sole source of retinal dopamine is dopaminergic amacrine cells (DACs). We and others have previously demonstrated that DACs are activated by rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs) upon illumination. However, it is still not clear how each class of photosensitive cells generates light responses in DACs. We genetically isolated cone function in mice to specifically examine the cone-mediated responses of DACs and their neural pathways. In addition to the reported excitatory input to DACs from light-increment (ON) bipolar cells, we found that cones alternatively signal to DACs via a retrograde signalling pathway from ipRGCs. Cones also produce ON and light-decrement (OFF) inhibitory responses in DACs, which are mediated by other amacrine cells, likely driven by type 1 and type 2/3a OFF bipolar cells, respectively. Dye injections indicated that DACs had similar morphological profiles with or without ON/OFF inhibition. Our data demonstrate that cones utilize specific parallel excitatory and inhibitory circuits to modulate DAC activity and efficiently regulate dopamine release and the light-adaptive state of the retina.
Highlights
Dopamine is a key neurotransmitter in the retina and plays a central role in the light adaptive processes of the visual system
It is unlikely that dopaminergic amacrine cells (DACs) are compromised by the loss of rod and melanopsin function because their density remained unchanged compared to wild-type mice
We have demonstrated that (1) cones alone generate three classes of light responses in DACs: an excitatory ON response, a delayed inhibitory ON response, and an inhibitory OFF response; (2) the excitatory ON responses are mediated by ON bipolar cells both directly and indirectly, via intrinsically photosensitive retinal ganglion cells (ipRGCs); (3) the inhibitory ON response is mediated by glycinergic amacrine cells that are likely driven by OFF bipolar cells expressing the amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor; (4) the inhibitory OFF response is mediated by GABAergic/glycinergic amacrine cells that appear to be driven by OFF bipolar cells expressing the kainate receptor; (5) DACs with distinct light responses have indistinguishable morphological profiles; and (6) dopamine release is triggered by light in the cone-function-only eye
Summary
Dopamine is a key neurotransmitter in the retina and plays a central role in the light adaptive processes of the visual system. We and others have previously demonstrated that DACs are activated by rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs) upon illumination. It is still not clear how each class of photosensitive cells generates light responses in DACs. We genetically isolated cone function in mice to examine the cone-mediated responses of DACs and their neural pathways. Cones are known to use parallel ON and OFF pathways that provide information about increases and decreases in light levels, respectively The cones transmit their signals through bipolar cells to amacrine and ganglion cells. This problem is difficult to solve, because mouse cone signals cannot be distinguished from rod signals based on stimulation wavelength or intensity (Mouse cones do not express a long-wavelength opsin, but an opsin sensitive to middle wavelengths with a peak at 510 nm, greatly overlapping with that of the rods[22])
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