Dopamine D1 Receptors Modulate glycinergic Inhibitory Inputs to OFF cone bipolar cells elicited by Optogenetic Activation of Amacrine Cells

Light evoked inhibition on OFF cone bipolar cells has been shown to be modulated by both background light levels and the Dopamine D1 Receptor. Since dopamine receptors are localized throughout the mouse retina, it is not known where in the light signaling cascade dopamine is modulating signals to OFF bipolar cells. The goal of this work was to develop a technique that allowed for the isolation of the amacrine to OFF bipolar cell circuit and determine if there are local changes in inhibition elicited by presynaptic amacrine cells onto OFF bipolar cells. To do this, we utilized the B6.Cg-Tg(Slc32al-COP4*H134R/EYFP) mouse line. These mice contain ChR2 in all the inhibitory cells in the retina. By optogenetically activating the amacrine cells, we were able to elicit inhibitory currents on bipolar cells independent of photoreceptor activation. Additionally, we were able to pharmacologically block inputs from photoreceptors while simultaneously isolating individual GABAergic and glycinergic inputs to OFF bipolar cells. While these optogenetically elicited currents were distinct from previously recorded light evoked currents, we found this as an effect way to measure changes in SKF38393 mediated reductions in glycinergic currents on OFF bipolar cells. However, we did not observe changes in GABAergic inhibition as we have previously seen in light evoked currents. Together, this gives a novel perspective on how dopamine differentially shapes inhibitory changes in the inner retina.