Chronic environmental or genetic elevation of galanin in noradrenergic neurons confers stress resilience in mice

Tillage, Rachel P; Wilson, Genevieve E.; Liles, L. Cameron; Holmes, Philip V.

doi:10.1101/2020.04.24.060608

Cited by 11 publications

(16 citation statements)

References 58 publications

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“…The foot shock stress protocol was conducted as described previously (27). Mice were individually exposed to 20 min of foot shock consisting of 19 shocks randomly interspaced by 30, 60 or 90 s (0.5 ms shocks, 1 mA) in chambers (Coulbourn Instruments, Holliston, MA) with an electric grid shock floor.…”

Section: Stress Paradigmmentioning

confidence: 99%

“…Control animals were placed in the chamber for 20 min but were not administered shocks. Corticosterone (CORT) measurement was conducted as described (27) (see supplement for details).…”

Section: Stress Paradigmmentioning

confidence: 99%

Section: Optogenetics and Ezm Testingmentioning

confidence: 99%

“…Stereotaxic viral and optic ferrule surgeries were performed as described previously (27) (see supplement for details). LC optogenetic stimulation was based on a published paradigm used in our lab previously (27,28). Photostimulation was delivered to the LC for 30 min (5 Hz tonic stimulation, 10 ms light pulses, 473 nm) in 3 min on/off bins in the home cage immediately before testing in the EZM, which was conducted as previous described (18).…”

Section: Optogenetics and Ezm Testingmentioning

confidence: 99%

“…Histology in mice used for optogenetics was performed as described (27) (see supplement for details).…”

Section: Optogenetics and Ezm Testingmentioning

confidence: 99%

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Co-released Norepinephrine and Galanin Act on Different Timescales to Promote Stress-Induced Anxiety-Like Behavior

Tillage

Foster

Lustberg

et al. 2020

Preprint

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BackgroundBoth the noradrenergic and galaninergic systems have been implicated in stress-related neuropsychiatric disorders, and these two neuromodulators are co-released from the stress-responsive locus coeruleus (LC); however, the individual contributions of LC-derived norepinephrine (NE) and galanin to behavioral stress responses are unclear. Here we aimed to disentangle the functional roles of co-released NE and galanin in stress-induced behavior.MethodsWe used foot shock, optogenetics, and behavioral pharmacology in wild-type (WT) mice and mice lacking either NE (Dbh-/-) or galanin (GalcKO-Dbh) specifically in noradrenergic neurons to isolate the roles of these co-transmitters in regulating anxiety-like behavior in the elevated zero maze (EZM) either immediately or 24 h following stress.ResultsFoot shock and optogenetic LC stimulation produced immediate anxiety-like behavior in WT mice, and the effects of foot shock persisted for 24 h. NE-deficient mice were resistant to the anxiogenic effects of acute stress and optogenetic LC stimulation, while mice lacking noradrenergic-derived galanin displayed typical increases in anxiety-like behavior. However, when tested 24 h after foot shock, both Dbh-/- and GalcKO-Dbh mice lacked normal expression of anxiety-like behavior. Pharmacological rescue of NE, but not galanin, in knockout mice during EZM testing was anxiogenic. In contrast, restoring galanin, but not NE, signaling during foot shock normalized stress-induced anxiety-like behavior 24 h later.ConclusionsThese results indicate that NE and noradrenergic-derived galanin play complementary, but distinguishable roles in behavioral responses to stress. NE is required for the expression of acute stress-induced anxiety, while noradrenergic-derived galanin mediates more persistent responses following a stressor.

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Section: Stress Paradigmmentioning

confidence: 99%

“…Control animals were placed in the chamber for 20 min but were not administered shocks. Corticosterone (CORT) measurement was conducted as described (27) (see supplement for details).…”

Section: Stress Paradigmmentioning

confidence: 99%