Electrical synapses in rod and cone pathways of the mouse retina

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The mammalian retina is able to encode visual information over ~10 log units of light intensities. It therefore has evolved two types of photoreceptors: rods for vision under dim light and cones for vision under bright light and color vision. Electrical synapses (gap junctions) built from connexin proteins play an essential role in the most sensitive rod pathway, the primary rod pathway, and in cone pathways. In the primary rod pathway, dim light signals are mediated from rods to rod bipolar cells, which in turn contact AII amacrine cells. AII cells form homocellular gap junctions among each other, thereby optimizing signal-to-noise ratio when photons are scarce. AII cells send the rod signal via glycinergic synapses to OFF cone bipolar cells and via heterocellular gap junctions to ON cone bipolar cells. Interestingly, the rectification of these electrical synapses becomes weaker during light adaptation favoring signal flow from ON bipolar to AII amacrine cells in bright light.AII-AII gap junctions differ in ultrastructure and sensitivity to neuromodulators from AII-ON cone bipolar cell gap junctions although the structural basis for these differences is only partially understood. While it is believed that AII-AII gap junctions are composed of connexin36 (Cx36), composition and regulation of AII-ON cone bipolar cell gap junctions are still debated. We have evidence now that AII cells not only express Cx36 but also another connexin. We hypothesize that this connexin is involved in heterocellular AII gap junctions and makes these junctions sensitive to modulators, which may induce changes in synapse rectification in a light-dependent manner. Moreover, we recently found AII-AII and AII-ON cone bipolar cell gap junctions to deviate in their assembly mechanisms although the basis for this difference is not known so far. In this project, we thus aim to determine the molecular basis for the differences in structure, assembly, and light-dependent modulation of homo- and heterocellular AII gap junctions.Electrical synapses are also essential for cone pathways. Together with colleagues, we recently found that ON bipolar cells are not only coupled to the AII amacrine cell but also to another glycinergic small-field amacrine cell. Whether this coupling is light-dependent and which connexins underlie the coupling is not known so far. Thus, we aim to analyze the regulation of the coupling and to identify the connexins involved.To achieve our goals, various connexin-deficient mouse lines and mouse lines expressing EGFP-tagged connexins will be used for co-immunoprecipitation, tracer coupling experiments under different light conditions, and superresolution microscopy-based localization analyses. This will help to understand how electrically coupled retinal neurons are able to establish electrical synapses with different synaptic partners and how these synapses can be differentially modulated depending on ambient light levels.