2020 Fiscal Year Research-status Report
Mapping working memory networks in the Drosophila brain
| Project/Area Number |
18K06496
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| Research Institution | Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
堀内 純二郎 公益財団法人東京都医学総合研究所, 脳・神経科学研究分野, 主席研究員 (80392364)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Keywords | Learning and memory / Drosophila / Neural memory networks |
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| Outline of Annual Research Achievements |
During this funding period, we have been examining the nature of memory storage and forgetting in Drosophila. In Drosophila, associative memories are formed and stored in brain structures known as the mushroom bodies (MBs). The associative learning and memory paradigm we study is a Pavlovian association where flies learn and form memories of associations between specific odors and pain. Thus, both odor and pain sensory inputs must both converge in the MBs where plastic changes occur to form memories. These memories then influence subsequent behaviors. The overall goal of our studies is to determine where plasticity or memory occurs in the MBs. Does it occur in MB neurons that respond to different odors or do they occur in downstream neurons? In order to study this question, we have been mapping where plasticity occurs for different types of memories. Thus far, we have identified neurons with altered function during formation of long-term memories. Neurons with altered functions due to memory formation are called memory engram cells and our major finding is that old flies, which have defects in long-term memories, form engram cells similar to young flies. However, the engram cells that they form are recalled by inappropriate odors leading to a phenomenon called memory generalization. Using mathematical modeling of behavioral data, we have found that memory generalization is a general method by which forgetting occurs in Drosophila.
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| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
We are interested in determining where memory, which is thought to be stored in plastic synaptic changes in neuronal networks, occurs in the MBs. Currently we have identified neurons where plastic changes required for long-term memories occur. These neurons are known as long-term memory engram cells. While these types of engram cells have been identified before, we have analyzed engram cells in old flies which are defective for long-term memories. By studying engrams in old flies, we hoped to determine why memory is poor in old flies. We considered three possibilities. 1) Memory engrams may not be made in old flies. 2) Memory engrams may not be reactivated in old flies when memories should be recalled. 3) Memory engrams may be reactivated improperly in old flies. Among these possibilities, we found that memory engrams are formed in old flies, and are reactivated upon memory recall. However, we found that these engrams are also reactivated at inappropriate times, causing memory to become uncertain. Currently, publication of our results has been slightly delayed because of the coronavirus pandemic, but we will publish soon.
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| Strategy for Future Research Activity |
Previously, we characterized engram cells storing long-term memories in young and old flies. The next step in our work is to determine whether these long-term memory engrams are formed in MB cells that originally responded to the memory associated odor. In other words, are cells that originally responded to an odor converted into engram cells when the odor becomes associated with either positive or negative experiences? We are planning to study this question by developing a system where we can label neurons that respond to an odor before memory formation and label long-term memory engram cells after memory formation. We will then compare whether the two tags overlap or not. Currently our experiments and results have been slightly delayed because of the coronavirus pandemic.
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| Causes of Carryover |
The 843,643 yen remaining from my 2020 budget is because I missed some international meetings by covid19. I will use my remaining budget from 2021 to attend some international meetings.
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[Journal Article] Carbon Monoxide, a Retrograde Messenger Generated in Postsynaptic Mushroom Body Neurons, Evokes Noncanonical Dopamine Release.2020
Author(s)
Ueno K, Morstein J, Ofusa K, Naganos S, Suzuki-Sawano E, Minegishi S, Rezgui SP, Kitagishi H, Michel BW, Chang CJ, Horiuchi J, Saitoe M.
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Journal Title
J Neurosci.
Volume: 40
Pages: 3533-3548
DOI
Peer Reviewed / Int'l Joint Research
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