Ankyrin-B and ankyrin-G are required for synaptic integrity in the mouse outer retina

Retinal circuit assembly relies on the precise timing and positioning of key molecules between neuronal partners to mediate proper synapse formation. In the outer retina, horizontal cells (HCs) are important interneurons that make the first contacts with photoreceptors and begin to segregate visual information into two distinct pathways by selectively forming synapses to the different types of photoreceptors. Dendrites of HCs synapse exclusively to cone photoreceptors, whereas the axon terminal synapses to rod photoreceptors. Failure to properly form these early connections disrupts the downstream connectivity of other postsynaptic neurons and leads to abnormal visual function. Although these early events are critical for proper synapse development, little is known about how this process is coordinated in the outer retina. In the present study, we performed single-cell RNA sequencing and uncovered members of the cytoskeletal scaffolding family of ankyrins to be differentially expressed in HCs during development. Specifically, we found ankyrin-B to be highly expressed in HCs at early time points and ankyrin-G to be expressed at later stages. Genetic deletion of both ankyrin-B and ankyrin-G disrupts outer retinal synaptic integrity and leads to impaired in vivo retinal responses. In summary, our findings uncovered a new requirement for ankyrin-B and ankyrin-G in maintaining synaptic connectivity in the outer retina essential for normal visual function.