2019 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, 認知症・高次脳機能研究分野, 主席研究員 (80392364)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | Learning and Memory / Drosophila / Forgetting |
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| Outline of Annual Research Achievements |
I have been studying the nature of forgetting in Drosophila. Flies can learn to associate an odor with pain. We can test for memory of this association by measuring how vigorously flies avoid this odor. As the time between learning and testing increases, flies avoid this odor less and less, indicating that they gradually forget this association. I have examined whether forgetting consists of a stochastic loss of memory in an increasing subset of flies, or whether it consists of a gradual decrease in odor avoidance in all flies. Using behavioral and statistical tests, I have found that most flies retain memory over time, but display a reduced avoidance to the pain-associated odor. This suggests that forgetting does not consist of a loss of a memory, but instead consists of an increase in uncertainty regarding a memory. These results have profound implications on how memory evolved, and also explains how short-term and middle-term memories change over time. I am currently writing a manuscript on this work.
In addition, I contributed to a manuscript, “Carbon monoxide, a retrograde messenger generated in post-synaptic mushroom body neurons evokes non-canonical dopamine release” (Ueno et al., JNeurosci 2020 Apr 29;40(18):3533-3548). This manuscript identifies a novel mechanism for dopamine release during synaptic plasticity.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
I am currently studying how flies learn to associate different sensory stimuli that do not occur at the same time. If flies smell a new odor and are electrically shocked at the same time, they learn to associate the odor with pain, and subsequently avoid the odor. The mechanism for this association has been extensively studied. However, flies can form this association even if they are shocked some time after the odor is removed. Thus there must be some timing mechanism where flies remember the odor and are able to associate this odor with a later shock. We are studying the cellular and molecular pathways required for this timing mechanism.
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| Strategy for Future Research Activity |
1) Odor associations are formed and stored in a brain structure known as the mushroom bodies in flies. Mushroom bodies have output neurons called mushroom body output neurons (MBONs). We have identified several MBONs that are required for time delayed (trace) memory associations. We will examine how manipulating that activity of these MBONs increases and decreases the strength of trace associations.
2) We will determine whether formation of time-delayed trace associations require continuous neuronal activity in the mushroom bodies during the delay (similar to working memory in mammals), or whether there is an intracellular timing mechanism that is active during the delay.
3) We will complete previous work on long-term memory (LTM) engram cells in flies. LTM engram cells are neurons that store long-term memories in the brain. LTM decreases as flies age. We will study how aging affects LTM engram cells.
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| Causes of Carryover |
The 374,523 yen remaining from my 2019 budget is because I was unable to attend several international meetings. I plan to use my remaining budget from 2019 in the current year to attend these meetings.
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[Journal Article] Carbon Monoxide, a Retrograde Messenger Generated in Postsynaptic Mushroom Body Neurons, Evokes Noncanonical Dopamine Release2020
Author(s)
Ueno, K., Morstein, J., Ofusa, K., Naganos, S., Suzuki-Sawano, E., Minegishi, S., Rezgui, S.P., Kitagishi, H., Michel, B.W., Chang, C.J., 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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