| Budget Amount *help |
¥15,540,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥840,000)
Fiscal Year 2007: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2006: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥4,700,000 (Direct Cost: ¥4,700,000)
|
|---|
| Research Abstract |
Left-right (L-R) asymmetry is a fundamental feature of higher-order neural function. However, the molecular basis of brain asymmetry remains unclear. We recently reported L-R asymmetry of hippocampal circuitry caused by differential allocation of N-methyl-D-aspartate receptor (NMDAR) subunit GluRε2 (NR2B) in hippocampal synapses (Science, 2003).
Studies on ε1 (NR2A) knock-out (KO) mice. To investigate whether asymmetrical ε2 allocation is also related to the types of the postsynaptic cells, we compared postembedding immunogold labeling for ε2 in left and right Sch synapses on pyramidal cells and interneurons. To facilitate the detection of ε2 density difference, we used ε1 subunit KO mice, which have a simplified NMDA receptor subunit composition. We found that ε2 distribution was asymmetrical between left and right Sch-pyramidal cell but not Sch-interneuron synapses, indicating a postsynaptic cell-type dependent regulation of the asymmetry. Also, we found that, in ε1 subunit KO mice, the asymmetry of ε2 allocation results in left-right difference in NMDA receptor content and synaptic plasticity (J. Neurosci, 2005).
Studies on iv mice. Iv is a spontaneous mouse mutant that possesses a mutation in the gene encoding the motor protein, Left-right dynein (Lrd). Fifty percent of iv/iv mice exhibit situs inversus, whereas the rest are normal (situs solitus). We found that the iv mouse hippocampus exhibited right isomerism of the synaptic distribution of the ε2 subunit. This laterality defect of the hippocampus is independent of the laterality of visceral organs. Therefore, the mechanisms responsible for the specification of L-R asymmetry differ between visceral organs and the brain (PLOS One, 2008).
|
