Elimination of galanin synthesis in noradrenergic neurons reduces galanin in select brain areas and promotes active coping behaviors

• Published in: Brain Structure and Function 2020-03, Vol.225 (2), p.785-803
• Main Authors: Tillage, Rachel P., Sciolino, Natale R., Plummer, Nicholas W., Lustberg, Daniel, Liles, L. Cameron, Hsiang, Madeline, Powell, Jeanne M., Smith, Kathleen G., Jensen, Patricia, Weinshenker, David
• Format: Article
• Language: English
• Subjects: Adaptation, Psychological - physiology; Adrenergic Neurons - metabolism; Animals; Anxiety; Biomedical and Life Sciences; Biomedicine; Brain; Brain - metabolism; Cell Biology; Coping; Female; Galanin; Galanin - genetics; Galanin - metabolism; Gene Knock-In Techniques; Hippocampus - metabolism; Hypothalamus; Latency; Male; Mental disorders; Mesencephalon; Metabolites; Mice, Knockout; Motor skill learning; Neurology; Neurons; Neurosciences; Norepinephrine; Original Article; Pons; Pons - metabolism; Prefrontal cortex; Prefrontal Cortex - metabolism
• ISSN: 1863-2653; 1863-2661; 0340-2061
• DOI: 10.1007/s00429-020-02035-4

Accumulating evidence indicates that disruption of galanin signaling is associated with neuropsychiatric disease, but the precise functions of this neuropeptide remain largely unresolved due to lack of tools for experimentally disrupting its transmission in a cell type-specific manner. To examine the function of galanin in the noradrenergic system, we generated and crossed two novel knock-in mouse lines to create animals lacking galanin specifically in noradrenergic neurons ( Gal cKO–Dbh ). We observed reduced levels of galanin peptide in pons, hippocampus, and prefrontal cortex of Gal cKO–Dbh mice, indicating that noradrenergic neurons are a significant source of galanin to those brain regions, while midbrain and hypothalamic galanin levels were comparable to littermate controls. In these same brain regions, we observed no change in levels of norepinephrine or its major metabolite at baseline or after an acute stressor, suggesting that loss of galanin does not affect noradrenergic synthesis or turnover. Gal cKO–Dbh mice had normal performance in tests of depression, learning, and motor-related behavior, but had an altered response in some anxiety-related tasks. Specifically, Gal cKO–Dbh mice showed increased marble and shock probe burying and had a reduced latency to eat in a novel environment, indicative of a more proactive coping strategy. Together, these findings indicate that noradrenergic neurons provide a significant source of galanin to discrete brain areas, and noradrenergic-specific galanin opposes adaptive coping responses.