Layer-specific developmentally precise axon targeting of transient suppressed-by-contrast retinal ganglion cells (tSbC RGCs)

Abstract

The mouse retina encodes diverse visual features in the spike trains of more than 40 retinal ganglion cell (RGC) types. Each RGC type innervates a specific subset of the more than 50 retinorecipient brain areas. Our catalog of RGC types and feature representations is nearing completion. Yet, we know little about where specific RGC types send their information. Furthermore, the developmental strategies by which RGC axons choose their targets and pattern their terminal arbors remain obscure. Here we identify a genetic intersection (Cck-Cre and Brn3cCKOAP) that selectively labels transient Suppressed-by-Contrast (tSbC) RGCs, a member of an evolutionarily conserved functionally mysterious RGC subclass. We find that tSbC RGCs selectively innervate the dorsolateral and ventrolateral geniculate nuclei of the thalamus (dLGN and vLGN), the superior colliculus (SC), and the nucleus of the optic tract (NOT). They binocularly innervate dLGN and vLGN but project only contralaterally to SC and NOT. In each target, tSbC RGC axons occupy a specific sublayer, suggesting that they restrict their input to specific circuits. The tSbC RGC axons span the length of the optic tract by birth and remain poised there until they simultaneously innervate their four targets around postnatal day five. The tSbC RGC axons make no errors in choosing their targets and establish mature stratification patterns from the outset. This precision is maintained in the absence of Brn3c. Our results provide the first map of SbC inputs to the brain, revealing a narrow target set, unexpected laminar organization, target-specific binocularity, and developmental precision. Significance statementIn recent years, we have learned a lot about the visual features encoded by retinal ganglion cells (RGCs), the eyes output neurons. In contrast, we know little about where RGCs send their information and how RGC axons, which carry this information, target specific brain areas during development. Here, we develop an intersectional strategy to label a unique RGC type, the tSbC RGC, and map its projections. We find that tSbC RGC axons are highly selective. They innervate few retinal targets and restrict their arbors to specific sublayers within these targets. The selective tSbC RGC projection patterns develop synchronously and without trial and error, suggesting molecular determinism and coordination.