Ephrin-As and patterned retinal activity act together in the development of topographic maps in the primary visual system

The development of topographic maps in the primary visual system is thought to rely on a combination of EphA/ephrin-A interactions and patterned neural activity. Here, we characterize the retinogeniculate and retinocollicular maps of mice mutant for ephrins-A2, -A3, and -A5 ( the three ephrin-As expressed in the mouse visual system), mice mutant for the beta 2 subunit of the nicotinic acetylcholine receptor (that lack early patterned retinal activity), and mice mutant for both ephrin-As and beta 2. We also provide the first comprehensive anatomical description of the topographic connections between the retina and the dorsal lateral geniculate nucleus. We find that, although ephrin-A2/A3/A5 triple knock-out mice have severe mapping defects in both projections, they do not completely lack topography. Mice lacking beta 2-dependent retinal activity have nearly normal topography but fail to refine axonal arbors. Mice mutant for both ephrin-As and beta 2 have synergistic mapping defects that result in a near absence of map in the retinocollicular projection; however, the retinogeniculate projection is not as severely disrupted as the retinocollicular projection is in these mutants. These results show that ephrin-As and patterned retinal activity act together to establish topographic maps, and demonstrate that midbrain and forebrain connections have a differential requirement for ephrin-As and patterned retinal activity in topographic map development.