Budget Amount *help |
¥15,340,000 (Direct Cost: ¥11,800,000、Indirect Cost: ¥3,540,000)
Fiscal Year 2015: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2013: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
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Outline of Final Research Achievements |
Synapses are formed and maintained by trans-synaptic interaction between pre- and postsynaptic cell adhesion molecules. In the cerebellum, the trans-synaptic interaction of postsynaptic glutamate receptor GluRδ2 and presynaptic neurexins (Nrxns) through cerebellin precursor protein 1 (Cbln1) mediates parallel fiber (PF)-Purkinje cell (PC) synapse formation. In mammals, Nrxns are encoded by three genes (Nrxn1, Nrxn2, and Nrxn3). In this study, we generated cerebellar granule cell (GC)-specific Nrxn1, Nrxn2, and Nrxn3 triple KO mice. The cerebellar GCs-specific Nrxns triple KO mice showed severe ataxia and reduced cerebellar size. Histological analysis revealed that the number of cerebellar GCs was dramatically decreased in the cerebellar GCs-specific Nrxns triple KO mice. Electron microscopic analysis showed that PF-PC synapses were disappeared in the GCs-specific Nrxns triple KO mice. These results suggest that Nrxns are essential for cerebellar circuit formation.
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