Noradrenergic regulation of fear and extinction learning

• Project Area: Principles of memory dynamism elucidated from a diversity of learning systems
• Project/Area Number: 16H01291
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Institute of Physical and Chemical Research
• 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)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000); Fiscal Year 2017: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2016: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
• Keywords: Locus Coeruleus / Noradrenaline / fear / extinction / prefrontal cortex / amygdala / noradrenaline / locus coeruleus / learning and memory / fear learning / behavioral flexibility / Locus coeruleus

Outline of Annual Research Achievements

In the last fiscal year we examined how locus coeruleus noradrenaline neurons in the brainstem encode information when animals are learning to fear a sensory stimulus and when the animals realizes that the sensory stimulus is no longer threatening and reduce their fear responses (a process termed fear extinction). We found that some LC-noradrenaline neurons increased their firing rate in high fear states while others increased their response when animals realized they should no longer be afraid during extinction. In addition we found that LC-noradrenaline synaptic inputs to the amygdala are important for fear learning while synaptic innervation of the medial prefrontal cortex is important for extinction. Together with our previous results this showed that different populations of LC-noradrenaline neurons control fear and extinction learning.

Research Progress Status

29年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

29年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] A dopaminergic switch for fear to safety transitions (2018)
  • Author(s): Luo, R., Uematsu, A., Weitemier, A., Aquili, L., Koivumaa, J., McHugh, T.J. and Johansen, J.P.
  • Journal Title: Nature Communications Volume: In press
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Learning rules for aversive associative memory formation (2018)
  • Author(s): Ozawa, T. & Johansen, J.P.
  • Journal Title: Current Opinion in Neurobiology Volume: 49 Pages: 148-157
  • DOI: 10.1016/j.conb.2018.02.010
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dysregulation of aversive signaling pathways: a novel circuit endophenotype for pain and anxiety disorders (2017)
  • Author(s): Yeh, L.-F., Watanabe, M., Sulkes-Cuevas, J. Johansen, J.P.
  • Journal Title: Current Opinion in Neurobiology Volume: 48 Pages: 37-44
  • DOI: 10.1016/j.conb.2017.09.006
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Modular organization of the brainstem noradrenaline system coordinates opposing learning states (2017)
  • Author(s): Uematsu Akira、Tan Bao Zhen、Ycu Edgar A、Cuevas Jessica Sulkes、Koivumaa Jenny、Junyent Felix、Kremer Eric J、Witten Ilana B、Deisseroth Karl、Johansen Joshua P
  • Journal Title: Nature Neuroscience Volume: 20 Issue: 11 Pages: 1602-1611
  • DOI: 10.1038/nn.4642
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A feedback neural circuit for calibrating aversive memory strength (2017)
  • Author(s): Ozawa, T., Ycu, E.A., Kumar, A., Yeh. L-F., Ahmed, T., Koivumaa, J., and Johansen, J.P.
  • Journal Title: Nature Neuroscience Volume: 20(1) Issue: 1 Pages: 90-97
  • DOI: 10.1038/nn.4439
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] β-Adrenergic Receptors Regulate the Acquisition and Consolidation Phases of Aversive Memory Formation Through Distinct, Temporally Regulated Signaling Pathways (2017)
  • 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.
  • Journal Title: Neuropsychopharmacology Volume: 42(4) Issue: 4 Pages: 895-903
  • DOI: 10.1038/npp.2016.238
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Evaluation of ambiguous associations in the amygdala by learning the structure of the environment. (2016)
  • Author(s): Madarasz, T.J., Diaz-Mataix, L., Akhand, O., Ycu, E.A., LeDoux, J.E., Johansen, J.P.
  • Journal Title: Nature Neuroscience Volume: In press Issue: 7 Pages: 965-972
  • DOI: 10.1038/nn.4308
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Meta-organization in the locus coeruleus noradrenaline system coordinates emotional and flexible learning states (2016)
  • Author(s): Joshua Johansen
  • Organizer: Arrowhead 10 years on: What have we learned and what is there still to learn about the neural bases of decision-making?
  • Place of Presentation: Sydney, Australia
  • Year and Date: 2016-12-11
  • Invited
• [Presentation] Multiplexed signaling across distinct noradrenaline cell populations coordinates opposing emotional learning functions (2016)
  • Author(s): Joshua Johansen
  • Organizer: Nature Conference on Neural Circuitry of Emotion
  • Place of Presentation: Shenzhen, China
  • Year and Date: 2016-11-02
  • Invited
• [Presentation] Functional specificity based on efferent connectivity in the locus coeruleus noradrenaline system (2016)
  • Author(s): Joshua Johansen
  • Organizer: Japan Neuroscience Society Meeting Symposium (Chaired)
  • Place of Presentation: Pacifico Conference Center (Yokohama)
  • Year and Date: 2016-07-20
  • Int'l Joint Research / Invited
• [Presentation] Regulation of fear & extinction learning through distinct neuromodulatory circuits (2016)
  • Author(s): Joshua Johansen
  • Organizer: Federation of European Neuroscience Societies Symposium (Chaired)
  • Place of Presentation: Copenhagen, Denmark
  • Year and Date: 2016-07-02
  • Int'l Joint Research / Invited