研究課題
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.
3: やや遅れている
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.
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.
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.
すべて 2021 その他
すべて 雑誌論文 (1件) (うち国際共著 1件、 査読あり 1件、 オープンアクセス 1件) 備考 (1件)
SCIENCE ADVANCES
巻: Vol 7, Issue 46 ページ: eabl6077
10.1126/sciadv.abl6077
https://www.igakuken.or.jp/memory/index.html
