| Budget Amount *help |
¥19,630,000 (Direct Cost: ¥15,100,000、Indirect Cost: ¥4,530,000)
Fiscal Year 2015: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2014: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2013: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
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| Outline of Final Research Achievements |
Neurexins are pre-synaptic cell adhesion molecules that bind post-synaptic Neuroligins to induce synapse formation and maturation. Both Neurexins and Neuroligins are implicated in autism. We hypothesized that the synaptic defects caused by disruption of Neurexins-Neuroligins interaction may be involved in the molecular pathophysiology of autism. To test this hypothesis, we generated mutant mice of Neurexins that have deficit of Neurexin-Neuroligin binding and analyzed the effect on synapse functions. Neurexin-3 ss4+ knockin mice of which Neurexin-3 lacks binding affinity to Neuroligins decreased the AMPA receptor-mediated synaptic transmission in the hippocampal neurons due to the hyper-internalization of AMPA receptor from the post-synapitc membrane. This phenotype is consistent with that in Neuroligin-3 R704C autism model mice, suggesting that this may be the mechanism caused by impaired Neurexin-Neuroligin interaction associated with autism pathophysiology.
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