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

• Published in: Molecular psychiatry Vol. 24; no. 5; pp. 710 - 725
• Main Authors: Chen, Yu-Wei, Das, Manasmita, Oyarzabal, Esteban A., Cheng, Qing, Plummer, Nicholas W., Smith, Kathleen G., Jones, Grace K., Malawsky, Daniel, Yakel, Jerrel L., Shih, Yen-Yu Ian, Jensen, Patricia
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2019; Nature Publishing Group
• Subjects: 13/44; 13/51; 14/19; 14/32; 59/36; 631/208; 631/378; 64/60; 9/74; Adaptation, Psychological - physiology; Adrenergic Neurons - metabolism; Adrenergic Neurons - physiology; Amygdala; Amygdala - metabolism; Animal genetic engineering; Animals; Anxiety; Anxiety - genetics; Anxiety - metabolism; Behavior, Animal - physiology; Behavioral Sciences; Biological Psychology; Blood volume; Brain; Brain - metabolism; Brain mapping; Cerebral blood flow; Diagnostic imaging; Female; Functional magnetic resonance imaging; Genetic aspects; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; HOXB1 protein; Identification and classification; Locus coeruleus; Male; Medicine; Medicine & Public Health; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neuroimaging; Neurons; Neurons - metabolism; Neurophysiology; Neurosciences; Norepinephrine; Pharmacotherapy; Physiological aspects; Population genetics; Psychiatry; Psychological aspects; Stress; Stress (Psychology); Stress response; Stress, Physiological - genetics; Stria terminalis; Subpopulations
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/s41380-018-0245-8

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.