Neural circuits research on the prevention of spontaneous recovery of fear memory

• Project/Area Number: 16K19791
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Psychiatric science
• Research Institution: Showa Pharmaceutical University
• Principal Investigator: MATSUDA Shingo 昭和薬科大学, 薬学部, 助教 (80723246)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 恐怖記憶 / 恐怖消去 / 性差 / 神経回路

Outline of Final Research Achievements

Neural activation in the infralimbic cortex, dorsal CA3, and paraventricular nucleus of thalamus increased through extinction sessions in males. There were sex differences in neural activation in the dCA3, PVT, and anterior of BLA (BLAa). Based on our result from an experiment investigating c-fos expression following extinction sessions, we predicted an alteration of neural activation through extinction sessions. Although sample number were low, BLAp lesion by ibotenic acid tended to decrease a stability of remote extinction memory in males. Moreover, in preliminary study, MeA lesion also decreased the stability in males. Taken together, our results suggested that BLAp and MeA might regulate a stability of fear extinction.

Academic Significance and Societal Importance of the Research Achievements

外傷後ストレス障害やパニック障害など恐怖記憶と関連のある精神疾患の治療法の一つに曝露療法がある。曝露療法は世界中で広く用いられているが、未だに治療期間を決めるための客観的な指標はない。客観的な指標の確立に向け、本研究は曝露療法の動物実験モデル(恐怖消去トレーニング課題)を利用して、恐怖消去トレーニング日数の変化に伴う脳活動変化を調べ、扁桃体外側基底核後部と扁桃体中心核が恐怖消去トレーニング効果の安定性に関わる可能性が得られた。今後、本研究の成果がヒトでの曝露療法中の脳活動の変動を明らかにする研究へと繋がり、最終的に治療期間を決めるための客観的な指標の確立に結びつくことが期待される。

Research Products

• [Journal Article] Sex differences in the effects of adult short-term isolation rearing on contextual fear memory and extinction (2018)
  • Author(s): Matsuda S, Tohyama S, Mizutani A
  • Journal Title: Neuroscience Letters Volume: 687 Pages: 119-123
  • DOI: 10.1016/j.neulet.2018.09.030
  • Peer Reviewed
• [Journal Article] 恐怖消去の性差を担う分子機構 (2018)
  • Author(s): 松田真悟
  • Journal Title: 日本生物学的精神医学会誌 Volume: 29 Pages: 57-59
  • NAID: 130007685084
  • Peer Reviewed
• [Journal Article] Development of the fear regulation system from early adolescence to young adulthood in female mice. (2018)
  • Author(s): Matsuda S, Matsuzawa D, Ishii D, Tomizawa H, Shimizu E.
  • Journal Title: Neurobiology of Learning and Memory Volume: 150 Pages: 93-98
  • DOI: 10.1016/j.nlm.2018.03.007
  • Peer Reviewed
• [Presentation] 恐怖消去の性差を担う分子機構 (2017)
  • Author(s): 松田真悟
  • Organizer: 第39回日本生物学的精神医学会・第47回日本神経精神薬理学会 合同年会
• [Presentation] 恐怖消去抵抗性の分子機構解明に向けた基盤的研究 (2017)
  • Author(s): 松田真悟, 遠山卓, 村上由, 古屋裕理, 松澤大輔, 石井大典, 富澤はるな, 須藤文和,一戸紀孝, 清水栄司, 水谷顕洋
  • Organizer: 第10回ハイテクリサーチセンター報告会
  • Place of Presentation: 昭和薬科大学 (東京都町田市)
• [Presentation] なぜ恐怖関連疾患の有病率は女性の方が高いのか？ (2016)
  • Author(s): 松田真悟
  • Organizer: 薬物・精神・行動の会 6月例会
  • Place of Presentation: 東京慈恵医科大学 (東京都港区)
• [Presentation] Sex differences in dynamics of neural activation in fear extinction (2016)
  • Author(s): 松田真悟, 一戸紀孝, 須藤文和
  • Organizer: 第39回神経科学大会
  • Place of Presentation: パシフィコ横浜 (神奈川県横浜市)