| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Outline of Final Research Achievements |
Parvalbumin (PV) interneurons are essential for cognitive processes in the brain, but the molecular mechanisms mediating activity-dependent regulation of PV interneurons remain unclear. Neuropsin cleaves directly mature neuregulin 1 (NRG1), releasing the ligand moiety from the matrix and enabling it to trigger the phosphorylation of ErbB4. We show in mice that generation of epileptic seizure led to transiently elevated neuropsin activity, which accompany with an increased activities of NRG1-ErbB4 signaling and ErbB4-expressed PV interneurons. Neuropsin-knockout mice exhibited impaired signaling through mature NRG1 after seizure, reduced ErbB4-expressing PV interneuron activity, but increased excitatory pyramidal neuron activity. Kainic acid-induced gamma oscillations showed reduced power, reversed by the NRG1 ligand moiety, in hippocampus of neuropsin-knockout mice. Our results show that neuropsin regulates PV interneurons through NRG1-ErbB4 signaling during network activity.
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