Fig. 8.
Divergent synaptic circuits implement contextual modulation in the Off and On pathways of pDSGCs. a A model of the synaptic mechanism underlying contextual modulation in the Off pathway. Box at the top: Schematic shows the synaptic motif in the Off pathway that participate in contextual modulation. Off WACs provide direct GABAergic inhibition onto Off SACs to suppress the cholinergic excitation from these Off SACs onto pDSGCs. Schematics in the bottom: Activation of the contextually modulated synaptic circuitry in wild type mice under different stimulus conditions. The leading edges of the black bars of the drifting gratings are labeled with red dashed lines. During uniform grating, Off WAC–Off SAC inhibition is maximally activated by the continuous dark contour and causes the strongest suppression of DSGC response. This inhibitory connection is less activated when discontinuities are present between center and surround contours during compound gratings (direction-contrast and phase-contrast). As a result, DSGC response is less suppressed during the compound gratings. Such difference between uniform grating and compound gratings is disrupted in Gabra2 KO mice in which Off WAC–Off SAC inhibition is removed. b A model of the synaptic mechanism underlying contextual modulation in the On pathway. Box at the top: Schematic shows the relevant synaptic connections in the On pathway. On WACs provide contextually sensitive inhibitory inputs onto bipolar cells (BCs) presynaptic to On SACs. In wild type mice, this inhibitory connection is suppressed by the GABAergic inhibition from On SACs. Schematics in the bottom: The leading edges of the white bars of the drifting gratings are labeled with red dashed lines. Because of the On SAC–On WAC–On BC–On SAC synaptic motif, the pDSGC On response is weakly modulated by stimulus contexts. Such weak contextual modulation is enhanced in Vgat cKO mice in which On SAC–On WAC inhibition is disrupted, but not affected in Gabra2 cKO mice in which GABAA receptors of SACs are disrupted