Ankyrins are essential for synaptic integrity of photoreceptors in the mouse outer retina.

The mammalian visual system consists of two distinct pathways: rod- and cone-driven vision. The rod pathway is responsible for dim light vision whereas the cone pathway mediates daylight vision and color perception. The distinct processing of visual information begins at the first synapse of rod and cone photoreceptors. The unique composition and organization of the rod and cone synapse is what allows information to be parsed into the different visual pathways. Although this is a critical process for vision, little is known about the key molecules responsible for establishing and maintaining the distinct synaptic architecture of the rod and cone synapse. In the present study, we uncovered a new role for Ankyrins in maintaining the synaptic integrity of the rod and cone synapse. Loss of Ankyrin-B and Ankyrin-G results in connectivity defects between photoreceptors and their synaptic partners. Ultrastructure analysis of the rod and cone synapse revealed impaired synaptic innervation, abnormal terminal morphology, and disruption of synaptic connections. Consistent with these findings, functional studies revealed impaired SIGNFICANCE STATEMENT: The first synapse in the outer retina begins to process visual information into two distinct pathways. This is largely attributed to the different composition and organization of the rod and cone synapse. Although the structural integrity of the rod and cone synapse is critical for normal vision, little is known about the key molecules responsible for maintaining the unique structure of the different photoreceptor synapses. In this study, we demonstrate a new function for the cytoskeletal scaffolding proteins, Ankryin-B and Ankyrin-G in the mouse outer retina. We found Ankyrin-B and Ankyrin-G are both required for proper retinal connectivity, where loss of these molecules leads to synaptic defects and impaired retinal responses.