ReviewRegulation of neurological and neuropsychiatric phenotypes by locus coeruleus-derived galanin

- The neuropeptide galanin is expressed in most locus coeruleus (LC) neurons.
- LC-derived galanin influences neurological and neuropsychiatric phenotypes.
- Neuromodulatory actions of LC-derived galanin are mediated by GAL1.
- Neurotrophic actions of LC-derived galanin are mediated by GAL2.
- New tools and strategies to study LC-derived galanin are proposed.

Decades of research confirm that noradrenergic locus coeruleus (LC) neurons are essential for arousal, attention, motivation, and stress responses. While most studies on LC transmission focused unsurprisingly on norepinephrine (NE), adrenergic signaling cannot account for all the consequences of LC activation. Galanin coexists with NE in the vast majority of LC neurons, yet the precise function of this neuropeptide has proved to be surprisingly elusive given our solid understanding of the LC system. To elucidate the contribution of galanin to LC physiology, here we briefly summarize the nature of stimuli that drive LC activity from a neuroanatomical perspective. We go on to describe the LC pathways in which galanin most likely exerts its effects on behavior, with a focus on addiction, depression, epilepsy, stress, and Alzheimer׳s disease. We propose a model in which LC-derived galanin has two distinct functions: as a neuromodulator, primarily acting via the galanin 1 receptor (GAL1), and as a trophic factor, primarily acting via galanin receptor 2 (GAL2). Finally, we discuss how the recent advances in neuropeptide detection, optogenetics and chemical genetics, and galanin receptor pharmacology can be harnessed to identify the roles of LC-derived galanin definitively.This article is part of a Special Issue entitled SI: Noradrenergic System.