Elucidation of neural mechanisms underlying fear memory using DREADD
| Project/Area Number |
16H05371
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
吉田 隆行 北海道大学, 医学研究院, 助教 (60374229)
大村 優 北海道大学, 医学研究院, 講師 (80597659)
泉 剛 北海道大学, 医学研究科, 准教授 (60312360)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000)
Fiscal Year 2018: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2016: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
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| Keywords | セロトニン / 人工受容体 / PTSD / 恐怖記憶 / 海馬 / DREADD / 5-HT2C / 消去 / Grik4 / 神経科学 |
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| Outline of Final Research Achievements |
The main aim of the present study is to elucidate the involvement of hippocampal serotonergic systems in fear memory. Microinjection of 5-HT7 receptor antagonist into the rat ventral hippocampus significantly suppressed the expression of freezing behavior, an index of fear memory retrieval in the contextual fear conditioning test. Electrophysiological data indicated that the 5-HT7 receptor agonist increased the frequency of action potentials in the ventral hippocampal CA3 pyramidal neuron. In situ hybridization demonstrated that Htr7 mRNA was abundantly expressed in the CA3 compared with other subregions of the hippocampus. Furthermore, it is known that 5-HT2C receptor is expressed in the CA3 subregion. We found that 5-HT2C receptor knockout mice tended to show rapid within-session extinction of fear, but not between-session extinction, compared to wild-type littermates. Moreover, we established the methods (DREADD) to control the neural activity in the CA3.
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| Academic Significance and Societal Importance of the Research Achievements |
心的外傷後ストレス障害(PTSD)患者に対してはセロトニン再取り込み阻害薬(SSRI)が主に処方されているが、投薬治療に反応するのは半数程度に過ぎず、十分な効果を得られていない。さらに、その作用機序には不明な点が多く、治療法改善に向けての有力な手掛かりが無い状況が続いている。このように、恐怖記憶の神経基盤を解明し、効果的な治療法開発の方向付けを行うことが重要である。本研究はSSRIの作用機序の一端を解明すると同時に、恐怖記憶の神経メカニズムの詳細を部分的にではあるが明らかにしたものである。
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Report
(4 results)
Research Products
(8 results)
