| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Research Abstract |
Long-term potentiation (LTP) at excitatory synapses in the hippocampus and amygdala is considered to be a cellular mechanism underlying neural plasticity such as memory and learning. The N-methyl-D-aspartate type of glumatate receptor (NMDAR) plays a key role in the induction of LTP as well as learning. Phosphorylation-dependent changes in NMDAR function have a crucial role in dynamic modulation of neural circuitry. The NR2B subunit of the NMDAR is tyrosine-phosphorylated in the brain, with Tyr-1472 its major phosphorylation site. Mice with a knockin mutation of the Tyr-1472 site to phenylalanine (Y1472F) show that Tyr-1472 phosphorylation is essential for fear learning and amygdaloid synaptic plasticity. The knockin mice show impaired fear-related learning and reduced amygdaloid long-term potentiation. NMDA receptor-mediated CaMKII signaling is impaired in YF/YF mice. Electron microscopic analyses reveal that the Y1472F mutant of the NR2B subunit shows improper localization at synapses in the amygdala. Thus, Tyr-1472 phosphorylation is a key mediator of fear learning and amygdaloid synaptic plasticity. Next, functional properties of NR2B subunit-containing receptors were studied in the amygdala and the Cal region of the hippocampus. We have found that the NR2B subunit significantly contributes to synaptic transmission, and its contribution is greater in the LA than in the Cal region, and biophysical properties of NMDA receptors and the NR2B/NR2A ratio are different between the two brain regions. These results indicate that NR2B subunit-containing NMDA receptors accumulate on the synaptic site and responsible for the unique properties of synaptic function and plasticity in the amygdala.
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