研究課題
As we age, our memory decreases. This process is known as age-related memory impairment or AMI. We are studying AMI in Drosophila. In particular, we have found that changes in glial activity are responsible for age-related impairments in long-term memory.Neuronal activity varies during memory formation. During learning, neurons need to be active. However, after learning, memories are consolidated to form long-term memory. During this time, neurons need to be inactive. We have found that glia function to inhibit neuronal function during consolidation. Old flies have decreased glial activity, preventing them from consolidating memories. Currently we are examining what happens when neurons are active during consolidation. This work will help us understand why memory decreases as we age.
2: おおむね順調に進展している
We have recently found that long-term memory (LTM) formation requires increased transcription in glial cells. To determine what glial genes are required for LTM, we screened for glial genes induced after learning. We identified a gene, dEAAT1 that encodes a glial glutamate transporter, which functions to reduce glutamate at synapses. Since glutamate is a predominant excitatory neurotransmitter, this suggests that neuronal activity needs to be inhibited during memory consolidation.Expression of dEAAT1 decreases upon aging, suggesting that old flies are unable to inhibit neuronal activity during memory consolidation. To determine whether this is a cause of age-related impairments in LTM, we overexpressed dEAAT1 and found improvements in LTM in old flies.
In the next year, we will answer the following questions: 1) in what cell types does neuronal activity need to be inhibited during memory consolidation, and 2) why does neuronal activity need to be inhibited during memory consolidation?Cell types. We are using genetic methods to inhibit activity of various cell types during consolidation. We have preliminary evidence demonstrating that inhibiting dopaminergic activity during consolidation improves memory. We are planning to determine what sub-type of dopaminergic neurons are responsible for this effect.Why does neuronal activity need to be inhibited during memory consolidation? We will examine whether dEAAT1 expression affects cell death, forgetting, or sleep during memory consolidation.
当初予定していた予算より物品費については安価に入荷できたため、その分は翌年に繰り越すこととした。また、旅費については予定していた学会参加等を本年は見合わせ翌年に参加することとしたため。
来年度は行動実験に利用する遺伝子組換えバエ作成にかかわる物品費用として利用し、学会に参加予定があるため次年度使用額から充当する予定である。
すべて 2017 2016
すべて 雑誌論文 (3件) (うち国際共著 3件、 査読あり 3件、 オープンアクセス 1件、 謝辞記載あり 3件)
Elife
巻: 24:6 ページ: e21076
10.7554/eLife.21076
Nat Commun.
巻: 14:7 ページ: 13471-13485
10.1038/ncomms13471
Mol Brain.
巻: 9:37 ページ: 1-10
10.1186/s13041-016-0217-3
