Identification of neuron-glia signaling mechanisms required for synaptic plasticity and memory formation

2017 Fiscal Year Annual Research Report

• Project/Area Number: 15K06729
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: 堀内 純二郎 公益財団法人東京都医学総合研究所, 認知症・高次脳機能研究分野, 主席研究員 (80392364)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: glia / long-term memory / Drosophila

Outline of Annual Research Achievements

We have been investigating mechanisms involved in age-related memory impairment and forgetting using Drosophila as a model organism. We previously found that aging causes a defect in long-term memory (LTM), and proposed that this defect may be caused by an inability of old glial cells to inhibit neuronal activity during memory consolidation. To test this idea, we inhibited activity of various neuron types in the Drosophila brain and found that reducing activity of dopaminergic neurons improves memory consolidation in old flies. We confirmed these results by demonstrating that pharmacological inhibition of dopaminergic neurons during consolidation, but not during learning, improves long-term memory. We also measured neuronal activity of dopaminergic neurons during memory consolidation in young and old flies and found evidence indicating that specific dopaminergic neurons are more active during consolidation in old flies compared to consolidation in young flies. Previous studies have suggested that these dopaminergic neurons are associated with forgetting. Thus our results indicate that activity of dopaminergic neurons involved in forgetting are inhibited during memory consolidation. Old flies forget more than young flies because they are unable to inhibit activity of these dopaminergic neurons due to defects in glial activity.

Research Products

• [Journal Article] Two parallel pathways assign opposing odor valences during Drosophila memory formation (2018)
  • Author(s): Yamazaki, D., Hiroi, M., Abe, T., Shimizu, K., Minami-Ohtsubo, M., Maeyama, Y., Horiuchi, J., Tabata, T.
  • Journal Title: Cell Reports Volume: 22 Pages: 2346-2358
  • DOI: 10.1016/j.celrep.2018.02.012.
  • Peer Reviewed
• [Journal Article] A Drosophila ex vivo model of olfactory appetitive learning (2017)
  • Author(s): Suzuki-Sawano, E., Ueno, K., Naganos, S., Sawano, Y., Horiuchi, J., Saitoe, M.
  • Journal Title: Scientific Reports Volume: 7 Pages: 17725-17735
  • DOI: 10.1038/s41598-017-17955-1.
  • Peer Reviewed
• [Journal Article] Coincident postsynaptic activity gates presynaptic dopamine release to induce plasticity in Drosophila mushroom bodies (2017)
  • Author(s): Ueno, K., Suzuki, E., Naganos, S., Ofusa, K., Horiuchi, J., Saitoe, M.
  • Journal Title: Elife Volume: 24 Pages: 21076-21094
  • DOI: 10.7554/eLife.21076.
  • Peer Reviewed / Open Access