A diverse network of pericoerulear neurons controls arousal

Abstract

As the primary source of norepinephrine in the brain, the locus coeruleus (LC) plays a key role in regulating arousal. The tuning of LC noradrenergic neuron (LC-NE) activity by distant and local neuromodulatory networks is central to understanding arousal and anxiety in the brain; however, these systems often control the LC by unknown polysynaptic mechanisms. In this study, we explore the connectivity and function of a web of inhibitory pericoerulear (peri-LC) GABAergic neurons that integrate distant stimuli and control the LC. We used complimentary techniques in electrophysiology, optogenetics, chemogenetics, RNA sequencing, and viral tracing to characterize the anatomy and function of peri-LC neurons in wild-type and transgenic mice. We found that peri-LC neurons integrate a diverse set of inputs and control the activity of the LC, forming a crucial node for the regulation of arousal in the brain.