Orexin/hypocretin system modulates amygdala-dependent threat learning through the locus coeruleus

Robert M. Sears, Ann E. Fink, Mattis B. Wigestrand, Claudia R. Farb, Luis De Lecea, Joseph E. LeDoux

Research output: Contribution to journalArticle

Abstract

Survival in a dangerous environment requires learning about stimuli that predict harm. Although recent work has focused on the amygdala as the locus of aversive memory formation, the hypothalamus has long been implicated in emotional regulation, and the hypothalamic neuropeptide orexin (hypocretin) is involved in anxiety states and arousal. Nevertheless, little is known about the role of orexin in aversive memory formation. Using a combination of behavioral pharmacology, slice physiology, and optogenetic techniques, we show that orexin acts upstream of the amygdala via the noradrenergic locus coeruleus to enable threat (fear) learning, specifically during the aversive event. Our results are consistent with clinical studies linking orexin levels to aversive learning and anxiety in humans and dysregulation of the orexin system may contribute to the etiology of fear and anxiety disorders.

Original languageEnglish (US)
Pages (from-to)20260-20265
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number50
DOIs
StatePublished - Dec 10 2013

Keywords

  • Channelrhodopsin-2
  • Fear conditioning
  • Norepinephrine

ASJC Scopus subject areas

  • General

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