Molecular mechanisms underlying selective synapse formation of vertebrate retinal photoreceptor cells

In vertebrate central nervous systems (CNSs), highly diverse neurons are selectively connected via synapses, which are essential for building an intricate neural network. The vertebrate retina is part of the CNS and is comprised of a distinct laminar organization, which serves as a good model system to study developmental synapse formation mechanisms. In the retina outer plexiform layer, rods and cones, two types of photoreceptor cells, elaborate selective synaptic contacts with ON- and/or OFF-bipolar cell terminals as well as with horizontal cell terminals. In the mouse retina, three photoreceptor subtypes and at least 15 bipolar subtypes exist. Previous and recent studies have significantly progressed our understanding of how selective synapse formation, between specific subtypes of photoreceptor and bipolar cells, is designed at the molecular level. In the ON pathway, photoreceptor-derived secreted and transmembrane proteins directly interact in trans with the GRM6 (mGluR6) complex, which is localized to ON-bipolar cell dendritic terminals, leading to selective synapse formation. Here, we review our current understanding of the key factors and mechanisms underlying selective synapse formation of photoreceptor cells with bipolar and horizontal cells in the retina. In addition, we describe how defects/mutations of the molecules involved in photoreceptor synapse formation are associated with human retinal diseases and visual disorders.