Genetic identification of a population of noradrenergic neurons implicated in attenuation of stress-related responses

Mol Psychiatry. 2019 May;24(5):710-725. doi: 10.1038/s41380-018-0245-8. Epub 2018 Sep 13.


Noradrenergic signaling plays a well-established role in promoting the stress response. Here we identify a subpopulation of noradrenergic neurons, defined by developmental expression of Hoxb1, that has a unique role in modulating stress-related behavior. Using an intersectional chemogenetic strategy, in combination with behavioral and physiological analyses, we show that activation of Hoxb1-noradrenergic (Hoxb1-NE) neurons decreases anxiety-like behavior and promotes an active coping strategy in response to acute stressors. In addition, we use cerebral blood volume-weighted functional magnetic resonance imaging to show that chemoactivation of Hoxb1-NE neurons results in reduced activity in stress-related brain regions, including the bed nucleus of the stria terminalis, amygdala, and locus coeruleus. Thus, the actions of Hoxb1-NE neurons are distinct from the well-documented functions of the locus coeruleus in promoting the stress response, demonstrating that the noradrenergic system contains multiple functionally distinct subpopulations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adaptation, Psychological / physiology
  • Adrenergic Neurons / metabolism
  • Adrenergic Neurons / physiology*
  • Amygdala / metabolism
  • Animals
  • Anxiety / genetics
  • Anxiety / metabolism
  • Behavior, Animal / physiology
  • Brain / metabolism
  • Female
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neurons / metabolism
  • Stress, Physiological / genetics*


  • HOXB1 homeodomain protein
  • Homeodomain Proteins