Analysis of learning and forgetting mechanisms based on Dopamine and Co-transmitters

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06388
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 46010:Neuroscience-general-related
• Research Institution: Tokyo Metropolitan Institute of Medical Science (2023); The University of Tokyo (2021-2022)
• Principal Investigator: YAMAZAKI Daisuke 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, 研究員 (80588377)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ドーパミン / グルタミン酸 / GABA / 忘却

Outline of Final Research Achievements

Dopamine neurons can be classified into PPL1 and PAM neurons, which are necessary for aversive and appetitive learning in Drosophila olfactory memory formation, respectively. However, it has been reported that PPL1 activation after averisve learning disrupts aversive memory. To identify the responsible signaling for memory stability in Drosophila mushroom bodies which receive dopaminergic inputs, we searched for receptor genes required for forgetting in aversive and appetitive memory. We found mGluRA and GABA-A receptor (Rdl) as destabilizers for aversive and appetitive memory, respectively. In previous work, we have identified gamma neuron subtypes (CRE-p and CRE-n) in the mushroom body necessary for aversive and appetitive memory, respectively. Interestingly mGluRA functioned only in CRE-p neurons and Rdl did in CRE-n neurons. Finally we also found that glutamate and GABA signaling could be selectively processed in distinct gamma neuron subtypes under control of forgetting.

Free Research Field

神経生物学

Academic Significance and Societal Importance of the Research Achievements

ドーパミンニューロンが複数のトランスミッターを放出する現象は種を超えて報告されてきているが、それらの生理学的な意義については研究が進んでいなかった。本研究では、ドーパミンおよびドーパミンニューロンの活性が記憶形成に必須である一方、記憶形成後には記憶の不安定化する現象に着目し、セカンドトランスミッターが記憶の安定化制御に寄与することを明らかにした。また、各セカンドトランスミッターのシグナルはそれらの受容体を持つ細胞群で選択的に処理されることから、記憶種ごとに安定化の制御が独立している可能性についても示した点において、意義深い。