Lack of TrkB and TrkC signaling alters the synaptogenesis and maturation of mossy fiber terminals in the hippocampus.

We have studied the role of endogenous neurotrophins in the formation and maturation of intrinsic hippocampal connections in vivo and analyzed the dentate granule cell projections in both trkB-/- and trkC-/- mice. Immunohistochemistry against calbindin did not show major alterations in the distribution of granule cell axons, which were located exclusively in the hilus and the stratum lucidum. However, the thickness of the stratum lucidum (mossy fiber termination zone) and the density of mossy fiber terminals were reduced in the absence of TrkB signaling. Electron-microscopic analyses showed that the fine structure of mossy terminals was altered in both trkB-/- and trkC-/- mice. Mutant granule cell terminals were smaller than those in wild-type animals and showed a reduction in both the number of synaptic contacts and synaptic vesicles. Immunofluorescence assays demonstrated that the expression levels of most synaptic-associated proteins (v-SNAREs and t-SNAREs) were altered in the mossy fibers of trkB- and trkC-deficient mice. Our results therefore reveal that TrkB and TrkC signaling is required for the maturation of granule cell axons.