The analysis of synaptic plasticity induced by Pavlovian conditioning in Drosophila feeding neural circuits at the single cell level

• Project/Area Number: 16K18375
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurophysiology / General neuroscience
• Research Institution: National Institute of Information and Communications Technology
• Principal Investigator: Sakurai Akira 国立研究開発法人情報通信研究機構, 未来ICT研究所フロンティア創造総合研究室, 主任研究員 (50749041)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: シナプス可塑性 / 連合学習 / 記憶 / カルシウムイメージング / オプトジェネティクス / 摂食神経回路 / ショウジョウバエ / 脳・神経 / 生理学 / 遺伝学 / ライブイメージング / 神経科学 / 動物 / 昆虫

Outline of Final Research Achievements

In this study, we aimed at connecting synaptic plasticity to memory at the single cell level. For this purpose, we have established a novel conditioning protocol to associate somatosensory stimuli (CS) with a feeding behavior (proboscis extension) induced by sucrose stimulation (US) in Drosophila brain. After repeated pairing of the CS and US, a pair of command neurons that control feeding behavior (“Feeding neuron”) were activated to extend proboscis in response to the CS, whereas they were not before the conditioning. These results suggest that a new connection from the CS-conveying circuit to the feeding circuit was created at the Feeding neuron and/or upstream of the Feeding neuron. To pinpoint where the new connection is generated, we inactivated the Feeding neuron during conditioning, leading to suppression of the conditioned response. These results are consistent with an assumption that the new connection was formed, at least partly, on the Feeding neuron.

Academic Significance and Societal Importance of the Research Achievements

シナプス可塑性と記憶の因果関係の解明については、「現在、我々の前に立ちはだかっている最大の問題は、ミクロな研究と、マクロな脳機能の研究との間に横たわっている深い溝を、繋げていく方法が必ずしも明確でないことである（塚原仲晃、脳の可塑性と記憶）」と指摘されている。本研究では、Feeding neuronという同定された中枢単一神経細胞上のシナプス入力の変化によって記憶が形成されることが示唆された。そのため、遺伝子機能の操作を行いながら、そのシナプスをリアルタイム観察することで、連合学習の分子細胞メカニズムについて、ミクロからマクロまで横断的な理解が得られることが期待される。

Research Products

• [Presentation] Activation of feeding command neuron by conditioned stimulus alone after Pavlovian conditioning (2018)
  • Author(s): Akira Sakurai, Hiroaki Kojima, Motojiro Yoshihara
  • Organizer: 第41回日本神経科学大会
• [Presentation] Feeding command neuron is activated to trigger proboscis extension in response to conditioned stimulus alone after Pavlovian conditioning in Drosophila (2018)
  • Author(s): Akira Sakurai, Hiroaki Kojima, Motojiro Yoshihara
  • Organizer: Cold Spring Harbor Asia meeting "Latest Advances in Development and Function of Neuronal Circuits"
• [Presentation] Identification of primary modification sites in the Drosophila feeding neural circuit, which is responsible for behavioral change induced by Pavlovian conditioning (2018)
  • Author(s): Akira Sakurai, Hiroaki Kojima, Motojiro Yoshihara
  • Organizer: 第41回日本分子生物学会年会
• [Presentation] A new paradigm of Pavlovian conditioning for correlating synaptic plasticity to memory at the feeding command neuron in Drosophila (2017)
  • Author(s): Akira Sakurai, Hiroaki Kojima, Motojiro Yoshihara
  • Organizer: 第４０回 日本分子生物学会年会
• [Presentation] A neural correlate of Pavlovian conditioning in Drosophila brain (2016)
  • Author(s): Akira Sakurai, J. Troy Littleton, Hiroaki Kojima, Motojiro Yoshihara
  • Organizer: Society for neuroscience (46th annual meeting)
  • Place of Presentation: San Diego, USA
  • Year and Date: 2016-11-12
  • Int'l Joint Research