Autonomous turning of cerebellar granule cells in vitro by intrinsic programs.

ABSTRACT

External guidance cues play a role in controlling neuronal cell turning in the developing brain, but little is known about whether intrinsic programs are also involved in controlling the turning. In this study, we examined whether granule cells undergo autonomous changes in the direction of migration in the microexplant cultures of the early postnatal mouse cerebellum. We found that granule cells exhibit spontaneous and periodical turning without cell-cell contact and in the absence of external guidance cues. The frequency of turning was increased by stimulating the Ca(2+) influx and the internal Ca(2+) release, or inhibiting the cAMP signaling pathway, while the frequency was reduced by inhibiting the Ca(2+) influx. Granule cell turning in vitro was classified into four distinct modes, which were characterized by the morphological changes in the leading process and the trailing process, such as bifurcating, turning, withdrawing, and changing the polarity. The occurrence of the 1st and 2nd modes of turning was differentially affected by altering the Ca(2+) and cAMP signaling pathways. Collectively, the results demonstrate that intrinsic programs regulate the autonomous turning of cerebellar granule cells in vitro. Furthermore, the results suggest that extrinsic signals play a role as essential modulators of intrinsic programs.