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Orexin modulates behavioral fear expression through the locus coeruleus

Author

Listed:
  • Shingo Soya

    (University of Tsukuba)

  • Tohru M. Takahashi

    (University of Tsukuba
    Kanazawa University, Kanazawa)

  • Thomas J. McHugh

    (Laboratory for Circuit & Behavioral Physiology RIKEN Brain Science Institute, Wako)

  • Takashi Maejima

    (Kanazawa University, Kanazawa)

  • Stefan Herlitze

    (ND7/31, Ruhr-University Bochum)

  • Manabu Abe

    (Brain Research Institute, Niigata University, Asahimachi)

  • Kenji Sakimura

    (Brain Research Institute, Niigata University, Asahimachi)

  • Takeshi Sakurai

    (University of Tsukuba
    University of Tsukuba, Tsukuba
    University of Tsukuba)

Abstract

Emotionally salient information activates orexin neurons in the lateral hypothalamus, leading to increase in sympathetic outflow and vigilance level. How this circuit alters animals’ behavior remains unknown. Here we report that noradrenergic neurons in the locus coeruleus (NALC neurons) projecting to the lateral amygdala (LA) receive synaptic input from orexin neurons. Pharmacogenetic/optogenetic silencing of this circuit as well as acute blockade of the orexin receptor-1 (OX1R) decreases conditioned fear responses. In contrast, optogenetic stimulation of this circuit potentiates freezing behavior against a similar but distinct context or cue. Increase of orexinergic tone by fasting also potentiates freezing behavior and LA activity, which are blocked by pharmacological blockade of OX1R in the LC. These findings demonstrate the circuit involving orexin, NALC and LA neurons mediates fear-related behavior and suggests inappropriate excitation of this pathway may cause fear generalization sometimes seen in psychiatric disorders, such as PTSD.

Suggested Citation

  • Shingo Soya & Tohru M. Takahashi & Thomas J. McHugh & Takashi Maejima & Stefan Herlitze & Manabu Abe & Kenji Sakimura & Takeshi Sakurai, 2017. "Orexin modulates behavioral fear expression through the locus coeruleus," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01782-z
    DOI: 10.1038/s41467-017-01782-z
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