| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Research Abstract |
The aim of this research is to clear the regulatory system of NMDA receptor activity in neurons expressing GluN2B(NR2B/GluRA2). Based on our findings, we established the hypothesis that GluN2B is crucial for NMDA receptor activity in neurons expressing GluN2B, and verified it. We generated the inhibitory neuron-specific GluN2B-KO, excitatory neuon-specific GluN2B-KO in forebrain, and CA1 pyramidal cell selective GluN2B-KO mice. Inhibitory neuron-specific GluN2B-KO mice showed developmental defect, abnormal hind-limb reflex, and abnormal projection of climbing fiber in cerebellum. Forebrain-specific GluN2B-KO mice died within 2 weeks after birth. Even through NMDA receptor-mediated synaptic currents were diminished, they were detected in CA1 pyramidal cell selective GluN2B-KO mice. The result was different from that of CA3 pyramidal cell-specific GluN2B-KO. These results suggest that the regulation of NMDA receptor activity depends on the type of neurons. Meanwhile, we generated a KO mouse of CaMKIIβsubunit that is involved with synaptic plasticity, and obtained a new finding. We observed that Arc/Arg3. 1 was bound to the CaMKIIβin an activity dependent manner and regulated the surface GluA1 levels in individual synapses. Our findings suggest that a novel Arc/Arg3. 1-CaMKIIβinteraction, which is strengthened by inactivity, acts as an "inverse" synaptic tagging and capture, mediating specific resetting of the surface AMPA-R levels at inactive synapses of previously potentiated neurons, based on the history of synaptic activity and inactivity in individual synapses.
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