Orexin modulates behavioral fear expression through the locus coeruleus

• SOYA, Shingo

• Takahashi, Tohru M.

• McHugh, Thomas J.

• Maejima, Takashi

• Herlitze, Stefan

• Abe, Manabu

• Sakimura, Kenji

• SAKURAI, Takeshi

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 (NA LC 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, NA LC 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.

Journal

• Nature Communications

  Nature Communications 8 1606-, 2017-11

  Nature Research

Keywords

• General Physics and Astronomy
• General Biochemistry, Genetics and Molecular Biology
• General Chemistry
• Multidisciplinary

Details

• CRID: 1050001202626659968
• NII Article ID: 120007128779
• NII Book ID: AA12645905
• DOI: 10.1038/s41467-017-01782-z
• ISSN: 20411723
• HANDLE: 2241/00149247
• Web Site: https://tsukuba.repo.nii.ac.jp/records/44369
• Web Site: https://www.nature.com/articles/s41467-017-01782-z.pdf
• Web Site: https://www.nature.com/articles/s41467-017-01782-z
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN