Activity-dependent refinement of the developing visual system. A comparative study across retinal ganglion cell populations and target nuclei

Abstract

The formation of the mammalian visual system is a complex process that takes place in several phases and includes neurogenesis, axon guidance, axonal refinement and circuit assembly. The last stage of this process occurs after birth but before eye opening. During this period, axon terminals from retinal ganglion cells (RGCs) first extensively arborize in the different visual nuclei and then refine and establish appropriate connections. It is known that the spontaneous activity generated in the immature retina during perinatal ages plays an important role in this axonal refinement process but it is not clear to what extent such retinal activity differentially influences the refinement of the distinct populations of RGCs when they project to specific visual nuclei. To address this issue we have generated conditional mouse lines to alter spontaneous activity in different populations of RGCs and we have analyzed the projection patterns of RGCs in different visual nuclei in each of these mouse lines. Our results show that the alteration of spontaneous activity in RGCs affects axon refinement in the image-forming nuclei such as the lateral geniculate nucleus and the superior colliculus, supporting previous publications. Interestingly, we also observed that, although to a lesser extent than in the image-forming nuclei, retinal spontaneous activity correlation is important for the refinement of RGC axons in the non-image-forming nuclei such as the pretectal olive nucleus or the suprachiasmatic nucleus.