ABSTRACT Introduction The locus coeruleus (LC) is a compact nucleus of noradrenergic neurons in the brainstem. Despite its relatively small size, the LC has widespread axonal connections and serves as the primary source of noradrenaline (NA) throughout the central nervous system. The LC‐NA system plays a critical role in regulating cognitive and physiological processes, and its dysfunction has been implicated in various neurological and psychiatric disorders. Results This narrative review explores the anatomy, neurochemistry, and function of the LC‐NA system in both the healthy and diseased brain. We first provide a detailed overview of LC connectivity, highlighting its afferent and efferent projections and their implications for brain‐wide noradrenaline modulation. Next, we discuss the neurochemical properties of noradrenaline, emphasizing its synthesis, release dynamics, and receptor interactions. The core of this review focuses on the functional roles of the LC‐NA system, systematically addressing each function first in the healthy brain and then discussing associated disorders. Specifically, we explore the role of LC‐NA signaling in attention and arousal, stress, emotion and pain, memory, motion, and neuroprotection, followed by discussions on psychiatric disorders, cognitive dysfunctions, and neurodegenerative diseases that arise from its dysregulation. Lastly, we examine the involvement of the LC in epilepsy, highlighting how alterations in noradrenaline signaling contribute to seizure susceptibility and propagation. Conclusion By integrating anatomical, neurochemical, and functional perspectives, this review provides a comprehensive understanding of the LC‐NA system's role in brain function and its relevance as a therapeutic target in neurological and psychiatric disorders.
Caestecker et al. (2025) studied this question.