Presynaptic SNAP25 supports maturation of hippocampal mossy fiber-CA3 synapses.

Mossy fiber (MF)-CA3 synapses in the hippocampus play vital roles in learning and memory. MFs have characteristic giant boutons with thorny excrescences on the dendrites of CA3 pyramidal neurons. The mechanisms underlying the development of this complex synaptic specialization remain unclear. In the present study, the loss of synaptosomal-associated protein 25 (SNAP25)-a protein essential for regulated synaptic vesicular release-increased the density but decreased the size of MF boutons and altered the postsynaptic distribution of homer scaffolding protein 1. Three-dimensional correlative light and electron microscopy revealed that although axon targeting and synapse formation were unaffected, excrescences failed to develop in MF boutons, resulting in a smaller contact area between MF boutons and CA3 dendrites. Moreover, SNAP25-deficient boutons displayed abnormal intracellular profiles, such as the accumulation of large synaptic vesicles. These findings indicate that presynaptic SNAP25 is essential for the maturation and maintenance of specialized hippocampal giant boutons.