2021 Fiscal Year Research-status Report
Mapping memory pathways in the Drosophila brain
| Project/Area Number |
21K06403
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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) |
2021-04-01 – 2024-03-31
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| Keywords | Learning / Memory / Drosophila |
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| Outline of Annual Research Achievements |
While learning and memory have been extensively studied in many organisms including Drosophila, characterization of forgetting has been lagging. In Drosophila, forgetting has been measured using a memory retention curve or forgetting curve where avoidance of flies to an odor previously paired to electrical shocks is measured at various timepoints. Avoidance scores decrease as time progresses indicating that flies forget the association over time. However, the nature of this forgetting has been unclear. Is there a stochastic probability that a fly irreversibly and completely loses memory of an association? Or does forgetting consist of a gradual increase in uncertainty regarding a memory? We have been studying this question using behavioral assays and in combination with our cellular characterization of memory engrams, we propose that forgetting consists of a gradual increase in uncertainty about an association that results loss of specificity of a memory, a term we refer to as memory generalization.
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| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
In order to determine whether forgetting in Drosophila consists of a complete loss of an associative memory or a gradual decrease in memory uncertainty, we mathematically modelled behaviors as a function of memory and memory strength/uncertainty. We next tested flies twice consecutively in a memory task and examined whether flies that displayed lack of memory in the first memory recall test could later recall memory in the second recall test. By incorporating this data into our mathematical model, we concluded that flies can retain memory of an association over time, but the strength of this memory is reduced over time such that it has a decreased influence on behavior. This is consistent with an increase in uncertainty regarding an association over time, but not a complete loss of a memory. We are currently organizing our results into a manuscript.
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| Strategy for Future Research Activity |
Our results showing that forgetting consists of an increase in uncertainty is consistent with our cellular results showing that memory engrams are activated at inappropriate times in old flies. Thus, old flies show a phenomenon called memory generalization where associations made for a specific odor “leak” to become associated with other odors. This indicates that flies become unsure of which odor is associated with a particular painful or pleasant outcome. In the next year we plan to study how this phenomenon of memory generalization occurs at the cellular level.
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| Causes of Carryover |
In order to support our current findings and enable publication, I need to develop a second method of identifying memory engram cells. Because of the coronavirus pandemic progress towards this goal was slightly delayed and funds for this research remained unused. This year I plan to use these funds to solidify our memory engram results and prepare them for publication.
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[Journal Article] High-sucrose diets contribute to brain angiopathy with impaired glucose uptake and psychosis-related higher brain dysfunctions in mice.2021
Author(s)
Hirai S, Miwa H, Tanaka T, Toriumi K, Kunii Y, Shimbo H, Sakamoto T, Hino M, Izumi R, Nagaoka A, Yabe H, Nakamachi T, Shioda S, Dan T, Miyata T, Nishito Y, Suzuki K, Miyashita M, Tomoda T, Hikida T, Horiuchi J, Itokawa M, Arai M, Okado H.
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Journal Title
SCIENCE ADVANCES
Volume: Vol 7, Issue 46
Pages: eabl6077
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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