| Budget Amount *help |
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2020: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2017: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Outline of Final Research Achievements |
Microglial synaptic engulfment has been confirmed by histology; however, direct real-time evidence is lacking. We develop a novel in vitro system of neuron-glia cocultures in which microglia maintain highly ramified processes. Using the system, we examined how synaptic engulfment is controlled when the “eat-me” signal, complement C1q. C1q significantly increased synaptic engulfment when microglial surveillance was induced by elevated neuronal activity. To confirm our findings in vivo, we used a mouse model of febrile seizures in which microglia preferentially engulf inhibitory synapses, even though C1q are deposited on both excitatory and inhibitory synapses. We determined that sustained activity of inhibitory neurons after seizures induce the inhibitory synapse-specific engulfment. Thus, our findings suggest that complement-dependent synaptic engulfment is triggered and spatially controlled by neuronal activity.
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