Optimal frequency of perinatal retinal waves is essential for the precise wiring of visual axons in non-image forming nuclei

Abstract

The formation of the visual system is a complex multistep process that includes proper assembly between retinal ganglion cell (RGC) axon terminals and their relay neurons in the different visual nuclei of the brain. RGC axons reach the main image-forming nuclei (IFN) —the superior colliculus and the lateral geniculate nucleus— at perinatal stages and extensively arborize to then refine throughout the first postnatal weeks. Spontaneous activity generated in the immature retina plays an essential role in the fine tune refinement of exhuberant axonal arborizations but the molecular mechanisms underlying this activity-dependent remodeling process remain poorly characterized. RGC axons, in addition to innervate IFN, target non-image forming nuclei (NIFN), but the impact of spontaneous retinal activity in the development of these accessory nuclei has not yet been described. Here, by genetically altering spontaneous activity in the RGCs of mice we demonstrate that correlated retinal activity also shapes the connectivity of the non-image forming circuit and identify the transcriptional programs modulating this process. Together, our data contribute to a better understanding of the molecular mechanisms ruling activity-dependent axon refining in the building of visual circuits.

Distribution, development, and identity of retinal ganglion cells labeled in the Sert‐Cre reporter mouse

“…Here, we took advantage of a BAC‐transgenic Cre‐driver mouse line, Sert‐Cre , that was generated as part of the GENSAT project (Gong et al., 2003; Heintz, 2004). This Cre driver line labels a population of RGCs in the VT crescent of the mouse retina, and a number of groups, including us, have used this line to study ipsiRGC RGCs, their projections to the brain, their function, and their role in activity‐dependent synaptic remodeling (Koch et al., 2011; Negueruela et al., 2022; Sitko et al., 2018; Su et al., 2021). Here, we show that the majority of cells labeled in this trangenic line are indeed ipsiRGCs.…”