Fig. 2

Control of cerebellar granule cell migration by Ca²⁺ transients and cyclic nucleotide signaling in a layer-specific manner. a Schematic diagram showing the relationship between the sequence of cerebellar granule cell migration and the pattern of Ca²⁺ transients. 1–5 enclosed within black circles Stages of granule cell differentiation as it proceeds in ascending order along the migratory pathway: 1 the cell tangentially migrates at the fastest rate in the external granular layer (EGL), 2 the cell changes the direction of migration from tangential to radial, i.e. turns, in two different modes at the boundary between EGL and the molecular layer (ML), 3 the cell radially migrates along the Bergmann glial process, 4 the cell radially migrates within the internal granular layer (IGL), 5 the cell completes migration at the bottom of the IGL. Green arrow at each stage indicates the direction of migration, and its length reflects the migration speed. Red traces Typical patterns of Ca²⁺ transients at corresponding stage. The speed positively correlates with the frequency of Ca²⁺ transients. The mode of turning at stage 2 is determined as shown in b. At stage 5, the migration terminates approximately 10 min after loss of Ca²⁺ transients. Dotted line in the Ca ²⁺ trace Time of termination. b Different modes of granule cell turning controlled by Ca²⁺ and cyclic nucleotide signaling at stage 2. Stimulating Ca²⁺ release from internal Ca²⁺ stores or cyclic guanosine monophosphate (cGMP) signaling increases the occurrence of L-shape turning, which is characterized by turning of the tip of the leading process to a new direction. Movement of the soma follows the direction of the tip turning. In contrast, increasing Ca²⁺ influx via the voltage-gated Ca²⁺ channel (VGCC) or glutamate receptors (N-methyl-D-aspartate receptor, NMDAR) or stimulating cyclic adenosine monophosphate (cAMP) signaling increases the occurrence of T- or Y-shape turning, characterized by bifurcation of the leading process [55]. The relationship between the turning modes and the Ca²⁺ or cyclic nucleotide signaling is essentially the same as that in isolated granule cells [55] (color figure online)