1 The dark - adapted response threshold of OFF ganglion cells is not set by OFF bipolar cells 2 in the mouse retina

37 38 The nervous system frequently integrates parallel streams of information to encode a 39 broad range of stimulus strengths. In mammalian retina it is generally believed that signals 40 generated by rod and cone photoreceptors converge onto cone bipolar cells prior to reaching the 41 retinal output, the ganglion cells. Near absolute visual threshold a specialized mammalian retinal 42 circuit, the rod bipolar pathway, pools signals from many rods and converges on depolarizing 43 (AII) amacrine cells. However, whether subsequent signal flow to OFF ganglion cells requires 44 OFF cone bipolar cells near visual threshold remains unclear. Glycinergic synapses between AII 45 amacrine cells and OFF cone bipolar cells are believed to relay subsequently rod-driven signals 46 to OFF ganglion cells. However, AII amacrine cells also make glycinergic synapses directly 47 with OFF ganglion cells. To determine the route for signal flow near visual threshold, we 48 measured the effect of the glycine receptor antagonist, strychnine, on response threshold in fully 49 dark-adapted retinal cells. As shown previously, we found that response threshold for OFF 50 ganglion cells was elevated by strychnine. Surprisingly, strychnine did not elevate response 51 threshold in any subclass of OFF cone bipolar cell. Instead, in every OFF cone bipolar subclass 52 strychnine suppressed tonic glycinergic inhibition without altering response threshold. 53 Consistent with this lack of influence of strychnine, we found that the dominant input to OFF 54 cone bipolar cells in darkness was excitatory and the response threshold of the excitatory input 55 varied by subclass. Thus, in the dark-adapted mouse retina, the high absolute sensitivity of OFF 56 ganglion cells cannot be explained by signal transmission through OFF cone bipolar cells. 57 58 Abbreviations: glycine receptors – GlyRs; 59 60