Abstract
How do precise circuits form in the mammalian CNS? Eye-specific retino-LGN projections are a prominent model pathway for exploring this question and in particular, for exploring the role of neuronal activity in synaptogenesis and axonal refinement. Previous work has shown that eliminating spontaneous retinal activity can alter both the normal segregation and the maintenance of eye-specific retino-LGN projections. Whether the pattern of retinal activity is important for segregation, however, remains the focus of intense investigation. We addressed the general requirement for retinal cues in eye-specific retino-LGN segregation and maintenance in mutant mice that exhibit delayed axonal degeneration (Wallerian degeneration slow; Wlds mice). The Wlds mouse allows for complete eye removal (enucleation) and thus all retinal cues, without the normal accompanying loss of ganglion cell axons. We find that eye-specific pathways are formed and maintained normally in non-enucleated Wlds mice. The results of combined tracing/enucleation experiments in Wlds mice support the hypothesis that the retina is a source of instructive signals for the initial eye-specific segregation process and for maintaining eye-specific circuits in the period immediately following their segregation. Over time, however, retinal cues become decreasingly important, and eventually retinal cues are not required at all for maintenance of eye-specific connections in the LGN.