| 研究領域 | マルチスケール精神病態の構成的理解 |
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| 研究課題/領域番号 |
19H05234
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| 研究機関 | 国立研究開発法人理化学研究所 |
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研究代表者 |
JOHANSEN JOSHUA 国立研究開発法人理化学研究所, 脳神経科学研究センター, チームリーダー (80625351)
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| 研究期間 (年度) |
2019-04-01 – 2021-03-31
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| キーワード | PTSD / Fear Extinction / Anxiety / Noradrenaline / prefrontal cortex / locus coeruleus |
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| 研究実績の概要 |
An inability to extinguish fear memories related to trauma experience lies at the heart of post-traumatic stress disorder (PTSD). Dysregulation of the noradrenaline system underlies this. This year we examined the contribution of axonal inputs to the LC from different subregions of the medial prefrontal cortex (mPFC) during fear extinction. We found that projections from the dorsomedial PFC (dmPFC), a region important in producing and sustain fear responses, target a specific subregion of LC and inhibit extinction. Conversely, projections from the ventromedial PFC (vmPFC), a subregion important for facilitating fear extinction, target a separate LC subregion and facilitate extinction learning. This shows that specific mPFC subregions opposingly regulate extinction of emotional memories.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
We have made significant progress on grant related activity. How noradrenaline systems are controlled by forebrain cortical structures involved in cognitive evaluations of threat and emotions is a clinically important question related to PTSD. In this year we made significant progress toward understanding how different subregions of mPFC regulate the brainstem noradrenaline system while animals are learning to suppress fear responses. We adapted complex anatomical and optogenetic approaches to address these questions which set the stage for important future work. Furthermore we published a high impact review on this topic which cited this grant (Likhtik & Johansen, Nature Neuroscience 2019).
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| 今後の研究の推進方策 |
Having established an opposing role for different subregions of mPFC on fear extinction and elucidate its anatomical basis, we will now focus on the larger afferent input anatomy and how these inputs (including mPFC) control distinct channels of noradrenaline outflow from the locus coeruleus. We reported previously (Uematsu et al. Nat Neuro 2017) that locus coeruleus (LC) projections to mPFC facilitate fear extinction, while a separate population of LC cells projecting to amygdala oppose this process. In the next year we will use rabies virus tracing to map all afferent inputs onto these distinct cell populations. In addition, we will examine the effects of stress on the afferent connectivity of these inputs with a particular focus on mPFC control of LC.
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