Orexin/hypocretin system modulates amygdala-dependent threat learning through the locus coeruleus
Abstract
The hypothalamic orexin (hypocretin) system controls survival-related processes such as food intake, arousal, and stress. Here we show that orexins also play an important role in learning about stimuli that predict harm. We demonstrate that blocking orexin activity in the noradrenergic locus coeruelus (LC) reduces, whereas increasing its activity enhances, threat learning in a Pavlovian auditory threat conditioning paradigm. Moreover, we demonstrate a direct functional connection between orexin enhancement of LC activity and amygdala-dependent memory processes. Strong, aversive memories can lead to fear and anxiety disorders that have a negative impact on individuals and their quality of life. The orexin system may represent a unique treatment target for these disorders.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- December 2013
- DOI:
- 10.1073/pnas.1320325110
- Bibcode:
- 2013PNAS..11020260S