Functional analysis of Down's syndrome associated molecule in the cerebellum excitatory synapse formation

Abstract

The cerebellum represents a good model system to investigate the molecular machinery underlying the synapse development, including its initiation, maturation and elimination depending on the neuronal activity. Multiple climbing fibers (CFs, axons of Inferior olivary neurons) innervate single purkinje cell soma and make synaptic-contact in early developmental stage. As advance the stage, single CF (Winner-CF) strengthened depend on neural activity. This

　Winner-CF translocates to PC dendrites and makes more synapses at P9 and later developmental stage. On the other hand, other weak CFs are pruned. These synapse formation mechanisms are important to neural circuit and brain function. However, its molecular mechanisms are unrevealed. We show that Down's syndrome relation molecule (DSCAM) has an important role for CF synapse formation in cerebellum. 1) DSCAM was expressed at cerebellar neuron and glia. 2) vGluT2 puncta (CF synapses) were decreased in adult Dscam mutant mouse. 3) The relative height of vGluT2 puncta decreased in adult mutant mouse. 4) Bergmann glia processes were inaccessible to active zone of synapses at outer molecular layer in Dscam mutant mouse. 5) Synapse size and post synaptic density (PSD) length at outer molecular layer were shorter in Dscam mutant mouse. These results suggest that DSCAM plays the important roles for CF synapse formation.