Stage-specific control of neuronal migration by somatostatin

Developing neurons transiently express somatostatin and its receptors1,2,3, but little is known about their function at these early stages. As we thought that endogenous somatostatin might control the migratory behaviour of immature neurons, we have examined the effects of somatostatin in cerebellar granule cells of early postnatal mice, because these cells express all five types of somatostatin receptors before the initiation of their migration4,5. Here we show that somatostatin has opposite and stage-specific effects on the migration of cerebellar granule cells. Activation of somatostatin receptors increases the rate of granule cell migration near their birthplace, but decreases the rate near their final destination. Furthermore, somatostatin enhances the size and frequency of spontaneous Ca2+ fluctuations in the early phase of migration, whereas it eliminates spike-like Ca2+ transients in the late phase. Somatostatin-induced changes at both early and late phases are reversed by a blockade of K+ channel activity. These results indicate that somatostatin may provide an essential cue for accelerating the movement of granule cells in the early phase and for terminating the movement in the late phase through altering intracellular Ca2+ concentrations and K+ channel activity.