Prefrontal regulation or dysregulation of brainstem noradrenaline for emotional control
Publicly Offered Research
| Project Area | Constructive understanding of multi-scale dynamism of neuropsychiatric disorders |
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| Project/Area Number |
19H05234
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| Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
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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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2020: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2019: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
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| Keywords | Noradrenaline / Emotion / PTSD / Amygdala / medial prefrontal cortex / Learning & Memory / Locus Coeruleus / Prefrontal Cortex / Fear Extinction / Anxiety / prefrontal cortex / locus coeruleus / neuromodulation / emotion / anxiety disorder / stress |
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| Outline of Research at the Start |
We will study the neural mechanisms for how emotional fear responses are controlled when they are innapropriate and how this control is dysregulated in conditions such as post-traumatic stress and anxiety disorders. Specifically we will examine how the brain noradrenaline system is regulated by the medial prefrontal cortex, a brain region important in cognition and emotional control.
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| Outline of Annual Research Achievements |
Controlling and extinguishing memories of traumatic experiences is critical in the treatment of post-traumatic stress disorder and certain anxiety disorders. Dysregulation of the noradrenaline system occurs in PTSD and anxiety disorder patients, but the underlying mechanisms for this are unclear. In previous research related to this grant we showed that the locus coeruleus (LC), the major source of noradrenaline to the forebrain, contains distinct cell populations that project to the amygdala or medial prefrontal cortex (mPFC). In the last year we've established a retrograde monosynaptic rabies tracing approach in mice and rats to map the brainwide afferent inputs to these cell populations. We've found that both cell populations receive some common inputs, but certain connections are specific. Notably, amygdala projecting LC neurons preferentially receive recurrent inputs from the amygdala while mPFC projecting LC neurons preferentially receive afferents from the mPFC. This shows that recurrent connectivity is an important organizational feature of this modularly organized neuromodulatory system and provides a circuit mechanism for their unique response properties and functionality related to emotional learning and memory. We are now finalizing analysis of how stress alters this connectivity.
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| Research Progress Status |
令和2年度が最終年度であるため、記入しない。
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| Strategy for Future Research Activity |
令和2年度が最終年度であるため、記入しない。
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Report
(2 results)
Research Products
(25 results)
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[Journal Article] Locus coeruleus: a new look at the blue spot2020
Author(s)
Poe G.R., Foote S., Eschenko O., Johansen J.P., Bouret S., Aston-Jones G., Harley C.W., Manahan-Vaughan D., Weinshenker D., Valentino R, Berridge C., Chandler D.J., Waterhouse B., Sara S.J.
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Journal Title
Nature Reviews Neuroscience
Volume: 21
Issue: 11
Pages: 644-659
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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