2016 Fiscal Year Annual Research Report
Noradrenergic regulation of fear and extinction learning
Publicly Offered Research
| Project Area | Principles of memory dynamism elucidated from a diversity of learning systems |
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| Project/Area Number |
16H01291
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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, 脳科学総合研究センター, チームリーダー (80625351)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Keywords | noradrenaline / locus coeruleus / fear learning / behavioral flexibility |
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| Outline of Annual Research Achievements |
In Heisei 28 we have made tremendous progress. We examined the contribution of the contribution of the brainstem locus coeruleus/LC-noradrenaline system to fear and extinction learning. In the last year we used viral approaches to manipulate and trace the efferent connectivity of specific LC-noradrenaline cell populations to the amygdala or medial prefrontal cortex (mPFC). In anatomical studies we found that the LC contains distinct cell populations which project to amygdala or mPFC. We then used a retrograde virus approach to optogenetically inhibit either the LC-noradrenaline cells projecting to amygdala or mPFC. We found that inhibition of amygdala projecting LC neurons blocked fear learning. By contrast, inhibiting the mPFC projecting LC-noradrenaline cells reduced fear extinction learning. Interestingly, inhibition of the amygdala projecting cells enhanced extinction learning, suggesting opposing interactions between amygdala and mPFC projecting LC cells during extinction learning. Finally, we used another retrograde viral approach to map the brain-wide efferent connectivity of these amygdala and mPFC projecting LC-noradrenaline cell populations. We found that each innervated amygdala or mPFC and functionally related, neighboring brain regions, but did not project to other brain regions.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
Everything is proceeding smoothly.
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| Strategy for Future Research Activity |
In the next fiscal year we will record from LC-noradrenaline neurons during fear and extinction learning to determine whether LC neurons behave homogeneously or heterogeneously. For these recordings we will use optogenetic identification of LC-noradrenaline neurons to verify cellular identity. We will then determine whether the projection defined LC-noradrenaline cell populations we discovered this year differentially encode information.
This year we found that amygdala and mPFC projecting LC cells have somewhat specific efferent connectivity. In the next fiscal year we will examine whether the terminal innervation of amygdala or mPFC from these distinct LC cell populations regulates fear and extinction learning.
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[Journal Article] A feedback neural circuit for calibrating aversive memory strength2017
Author(s)
Ozawa, T., Ycu, E.A., Kumar, A., Yeh. L-F., Ahmed, T., Koivumaa, J., and Johansen, J.P.
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Journal Title
Nature Neuroscience
Volume: 20(1)
Pages: 90-97
DOI
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] β-Adrenergic Receptors Regulate the Acquisition and Consolidation Phases of Aversive Memory Formation Through Distinct, Temporally Regulated Signaling Pathways2017
Author(s)
Schiff, H.C., Johansen, J.P., Hou, M., Bush, D.E., Smith, E.K., Klein, J.E., LeDoux, J.E., Sears, R.M.
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Journal Title
Neuropsychopharmacology
Volume: 42(4)
Pages: 895-903
DOI
Peer Reviewed / Int'l Joint Research
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[Journal Article] Evaluation of ambiguous associations in the amygdala by learning the structure of the environment2016
Author(s)
Madarasz, T.J., Diaz-Mataix, L., Akhand, O., Ycu, E.A., LeDoux, J.E., Johansen, J.P.
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Journal Title
Nature Neuroscience
Volume: 19
Pages: 965-972
DOI
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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