K252a, an inhibitor of Trk, disturbs pathfinding of hippocampal mossy fibers

Hippocampal mossy fibers, which are the axons of dentate granule cells, are continuously generated owing to adult neurogenesis of granule cells. They extend exclusively into the stratum lucidum, a proximal layer of the CA3 pyramidal cells. We visualized the mossy fiber tracts by Timm histochemical staining and DiI labeling in the cultured hippocampal slices from newborn rats. The fibers were abnormally expanded when the slices were cultured in the presence of K252a, an inhibitor of the neurotrophin receptor Trk. Similar defasciculation was observed with an inhibitor of MEK, which is one of the signaling molecules downstream of Trk. This study suggests for the first time that Trk and the MEK pathway are required for mossy fiber pathfinding.