Distinct modes of neuronal migration in different domains of developing cerebellar cortex.

As postmitotic neurons migrate to their final destinations, they encounter different cellular microenvironments, but functional responses of migrating neurons to changes in local environmental cues have not been examined. In the present study, we used a confocal microscope on acute cerebellar slice preparations to examine real-time changes in the shape of granule cells, as well as the mode and rate of their migration as they transit different microenvironments. The rate of granule cell movement is fastest in the molecular layer, whereas their elongated somata and long leading processes remain in close contact with Bergmann glial fibers. Cell movement is slowest in the Purkinje cell layer after granule cells detach from the surface of Bergmann glia and the somata become transiently round, whereas the leading processes considerably shorten. Surprisingly, after entering the internal granular layer, granule cells re-extend both their somata and leading processes as they resume rapid movement independent of Bergmann glial fibers. In this last phase of migration, described here for the first time, most granule cells move radially for >100 micron (a distance comparable to that observed in the molecular layer) until they reach the deep strata of the internal granular layer, where they become rounded again and form synaptic contacts with mossy fiber terminals. These observations reveal that migrating neurons alter their shape, rate, and mode of movement in response to local environmental cues and open the possibility for testing the role of signaling molecules in cerebellar neurogenesis.