Circuit microendophenotypes for post-traumatic stress disorder

• Project Area: Unraveling micro-endophenotypes of psychiatric disorders at the molecular, cellular and circuit levels.
• Project/Area Number: 15H01301
• 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): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000); Fiscal Year 2016: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2015: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
• Keywords: amygdala / emotional learning / periaqueductal gray / prediction error / PAG / teaching signal / fear learning

Outline of Annual Research Achievements

We made great progress in Heisei 28. Our goal was to anatomically functionally map aversive shock outputs from the periaqueductal gray (PAG) to the lateral amygdala. Previously we identified pathways from the PAG to the centromedial and paraventricular thalamus. In the last year we optogenetically manipulated these pathways and found that the PAG to paraventricular thalamus, but not the PAG-centromedial thalamus, circuit was necessary for aversive shocks to produce fear learning. Furthermore, we performed viral based efferent mapping of the projections of the thalamus projecting PAG neurons and revealed their brainwide efferent arborization throughout the brain

In addition to examining this ascending aversive signaling pathway we also studied how sensory predictive cues inhibit this pathway during learning to set the strength of fear memories (learning asymptotes). Previously we found that a pathway from the central nucleus of the amygdala controlled this process. Last year, we identified a specific population of PAG cells which are important for setting learning asymptotes using viral tracing and optogenetic manipulation approaches. This work was published this year (Ozawa et al. Nature Neuroscience 2017).

Research Progress Status

28年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

28年度が最終年度であるため、記入しない。

Research Products

• [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
• [Journal Article] Alterations in the rostral ventromedial medulla after the selective ablation of mu-opioid receptor expressing neurons. (2016)
  • Author(s): Harasawa, I., Johansen, J.P., Fields, H.L., Porreca, F., Meng, I.D.
  • Journal Title: Pain Volume: 157(1) Issue: 1 Pages: 166-173
  • DOI: 10.1097/j.pain.0000000000000344
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Projection specificity in heterogeneous locus coeruleus cell populations: implications for learning and memory. (2015)
  • Author(s): Uematsu, A., Tan, B.Z., Johansen, J.P.
  • Journal Title: Learning & Memory Volume: 22 Issue: 9 Pages: 444-451
  • DOI: 10.1101/lm.037283.114
  • Peer Reviewed / Open Access / 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
• [Presentation] Neural circuit mechanisms for triggering and reversing aversive memories (2016)
  • Author(s): Joshua Johansen
  • Organizer: Neural mechanisms of decision making: achievements and new directions
  • Place of Presentation: CiNet Bldg Conference room, Osaka, Japan
  • Year and Date: 2016-02-03
  • Invited
• [Presentation] A feedback neural circuit for calibrating memory strength (2015)
  • Author(s): Joshua Johansen
  • Organizer: International Symposium on Optogenetics (Tokyo, Japan)
  • Place of Presentation: Akio Suzuki Memorial Hall, Tokyo, Japan
  • Year and Date: 2015-12-05
  • Invited
• [Presentation] Functional and anatomical specificity in locus coeruleus noradrenaline neurons (2015)
  • Author(s): Joshua Johansen
  • Organizer: Gordon Conference: Amygdala in health and disease
  • Place of Presentation: Easton, USA
  • Year and Date: 2015-08-04
  • Int'l Joint Research / Invited