Dopaminergic regulation of fear extinction learning

2016 Fiscal Year Annual Research Report

• Project/Area Number: 15H04264
• 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 – 2018-03-31
• Keywords: Dopamine / Fear extinction / Nucleus Accumbens

Outline of Annual Research Achievements

In Heisei 28 we made significant progress. In fear conditioning, and auditory stimulus is paired with an aversive shock and animals exhibit fear responses to the tone after learning. However, if the tone is presented repeatedly in the absence of shock fear responding is extinguished. We've been studying how the brain knows to extinguish fear responses and have focused on the ventral tegmental area (VTA) dopamine system as potentially signaling when shocks don't occur to initiate extinction. In the previous year we found that inhibition of VTA dopamine neurons during the shock omission period of extinction blocked extinction learning (animals continued to be afraid of the tone. Last year we examined which downstream circuits these VTA dopamine neurons signaled to engage extinction. To do this we expressed an inhibitory opsin in the VTA dopamine neurons and inhibited their terminals in the nucleus accumbens (NAc). We first used voltammetry to show that dopamine released was inhibited in the NAc with optical inhibition of dopamine nerve terminals in the NAc. We then inhibited dopamine nerve terminals in the NAc during the shock omission period of extinction and found that this manipulation reduced the long term retention of extinction memories.

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

Everything is going smoothly

Strategy for Future Research Activity

In the next fiscal year we will examine the contribution of ventral tegmental area (VTA) dopamine projections to the amygdala and medial prefrontal cortex (mPFC) on fear and extinction learning. We will use a tyrosine hydroxylase-cre recombinase rat to express inhibitory opsins (Archaerhodopsin) in the VTA dopamine cells and their nerve terminals in the amygdala and mPFC. We will then inhibit the terminals of these cells in the amygdala and mPFC during either the shock period of fear conditioning or during the shock omission period of extinction and determine the effects of these manipulations on fear and extinction learning.

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) 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) 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: 19 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 – 2016-12-15
  • 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 – 2016-11-04
  • 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: Yokohama, Japan
  • Year and Date: 2016-07-20 – 2016-07-22
  • 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 – 2016-07-06
  • Int'l Joint Research / Invited