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In wild-type mice axons of retinal ganglion cells establish topographicallyprecise projection to the superior colliculus of the midbrain. This impliesthat axons of neighboring retinal ganglion cells project to the proximallocations in the target. The precision of topographic projection is a result ofcombined effects of molecular labels, such as Eph receptors and ephrins, andcorrelated electric activity. In the Isl2/EphA3 mutant mice the expressionlevels of molecular labels is changed. As a result the topographic projectionis rewired so that the neighborhood relationships between retinal cell axonsare disrupted. Here we argue that the effects of correlated activity presentingthemselves in the form of Hebbian learning rules can facilitate the restorationof the topographic connectivity even when the molecular labels carryconflicting instructions. This occurs because the correlations in electricactivity carry information about retinal cells' spatial location that isindependent on molecular labels. We argue therefore that experiments inIsl2/EphA3 knock-in mice directly test the interaction between effects ofmolecular labels and correlated activity during the development of neuralconnectivity.

Sperry versus Hebb: Topographic mapping in Isl2/EphA3 mutant mice