Anatomically and functionally distinct locus coeruleus efferents mediate opposing effects on anxietylike behavior

Olga Borodovitsyna, Brenna C Duffy, Anthony E Pickering, Daniel J Chandler

Research output: Contribution to journalArticle (Academic Journal)peer-review

24 Citations (Scopus)
223 Downloads (Pure)


The locus coeru (LC) is a critical node in the stress response, and its activation has been shown to promote hypervigilance and anxiety-like behavior. This noradrenergic nucleus has historically been considered homogeneous with highly divergent neurons that operate en masse to collectively affect central nervous system function and behavioral state. However, in recent years, LC has been identified as a heterogeneous structure whose neurons innervate discrete terminal fields and contribute to distinct aspects of behavior. We have previously shown that in late adolescent male rats, an acute traumatic stressor, simultaneous physical restraint and exposure to predator odor, preferentially induces c-Fos expression in a subset of dorsal LC neurons and persistently increases anxiety-like behavior. To investigate how these neurons respond to and contribute to the behavioral response to stress, we used a combination of retrograde tracing, whole-cell patch clamp electrophysiology, and chemogenetics. Here we show that LC neurons innervating the central nucleus of the amygdala (CeA) and medial prefrontal cortex (mPFC) undergo distinct electrophysiological changes in response to stressor exposure and have opposing roles in mediating anxiety-like behavior. While neurons innervating CeA become more excitable in response to stress and promote anxiety-like behavior, those innervating mPFC become less excitable and appear to promote exploration. These findings show that LC neurons innervating distinct terminal fields have unique physiological responses to particular stimuli. Furthermore, these observations advance the understanding of the LC as a complex and heterogeneous structure whose neurons maintain unique roles in various forms of behavior.
Original languageEnglish
Article number100284
Number of pages15
JournalNeurobiology of Stress
Early online date5 Dec 2020
Publication statusE-pub ahead of print - 5 Dec 2020

Structured keywords

  • Anaesthesia Pain and Critical Care


  • locus coeruleus
  • stress
  • central nucleus of amygdala
  • medial prefrontal cortex
  • anxiety-like behavior


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