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Sheng-Nan Qiao, Yong-Mei Zhong, Dao-Qi Zhang; Cone photoreceptors generate inhibitory ON and OFF responses in dopamingergic amacrine cells via distinct OFF pathways. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© ARVO (1962-2015); The Authors (2016-present)
Dopaminergic amacrine cells (DACs) are stimulated by photoreceptors to release dopamine, which plays a critical role in retinal light adaptation. Cone photoreceptors transmit light signals to amacrine cells via parallel ON and OFF pathways. Previous studies reported that DACs are excited by ON bipolar cells, but it is unclear whether DACs receive input from OFF bipolar cells. Here we determine how the OFF pathway regulates the DAC activity.
We utilized a transgenic mouse model lacking rod and melanopsin function in which retinal DACs were labeled with red fluorescence protein. Light responses of DACs were recorded under voltage clamp.
With 470-nm light stimuli, DACs (Vh= -66 mV) displayed three classes of light responses: an initial ON response, a delayed ON (d-ON) response and an OFF response. When L-AP4 was used to block ON pathways, the OFF and d-ON responses persisted while the ON response was blocked, indicating that the OFF and d-ON responses are mediated by the OFF pathway. The current-voltage relations showed that reverse potentials of the OFF and d-ON responses were around -50 mV (close to the equilibrium potential of Cl-) suggesting that OFF bipolar cells mediate inhibitory OFF and d-ON responses indirectly. Additionally, the OFF response was blocked by ACET, a kainate (KA) receptor antagonist, indicating that the OFF response is mediated by OFF bipolar cells expressing the KA receptor. In contrast, the d-ON response was not affected by ACET but blocked by additional CNQX, a KA/AMPA receptor antagonist, indicating that the d-ON response is mediated by OFF bipolar cells expressing the AMPA receptor. Furthermore, the OFF response was inhibited by both GABAzine and strychnine, indicating that this response is mediated by GABAergic and glycinergic amacrines. The d-ON response was eliminated by strychnine but not GABAzine, suggesting that glycinergic amacrines mediate the d-ON response.
OFF bipolar cells are reported to express different combinations of glutamate receptors: type 1 express the AMPA receptor, type 2 and 3a express the KA receptor and type 3b and 4 express both receptors. Therefore, our data suggests that the OFF response is mediated by type 2 and 3a OFF bipolar cells through GABAergic and glycinergic amacrine cells, whereas the d-ON response is mediated by type 1 OFF bipolar cells through glycinergic amacrine cells.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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