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- Title
Noradrenaline release from the locus coeruleus shapes stress-induced hippocampal gene expression.
- Authors
Privitera, Mattia; von Ziegler, Lukas M.; Floriou-Servou, Amalia; Duss, Sian N.; Runzhong Zhang; Waag, Rebecca; Leimbacher, Sebastian; Sturman, Oliver; Roessler, Fabienne K.; Heylen, Annelies; Vermeiren, Yannick; Van Dam, Debby; De Deyn, Peter P.; Germain, Pierre-Luc; Bohacek, Johannes
- Abstract
Exposure to an acute stressor triggers a complex cascade of neurochemical events in the brain. However, deciphering their individual impact on stress-induced molecular changes remains a major challenge. Here, we combine RNA sequencing with selective pharmacological, chemogenetic, and optogenetic manipulations to isolate the contribution of the locus coeruleus-noradrenaline (LC-NA) system to the acute stress response in mice. We reveal that NA release during stress exposure regulates a large and reproducible set of genes in the dorsal and ventral hippocampus via ß-adrenergic receptors. For a smaller subset of these genes, we show that NA release triggered by LC stimulation is sufficient to mimic the stress-induced transcriptional response. We observe these effects in both sexes, and independent of the pattern and frequency of LC activation. Using a retrograde optogenetic approach, we demonstrate that hippocampus-projecting LC neurons directly regulate hippocampal gene expression. Overall, a highly selective set of astrocyte-enriched genes emerges as key targets of LC-NA activation, most prominently several subunits of protein phosphatase 1 (Ppp1r3c, Ppp1r3d, Ppp1r3g) and type II iodothyronine deiodinase (Dio2). These results highlight the importance of astrocytic energy metabolism and thyroid hormone signaling in LC-mediated hippocampal function and offer new molecular targets for understanding how NA impacts brain function in health and disease.
- Subjects
LOCUS coeruleus; GENE expression; HIPPOCAMPUS (Brain); NORADRENALINE; PHOSPHOPROTEIN phosphatases; DRUG target; THYROID hormone receptors; BETA adrenoceptors
- Publication
eLife, 2024, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.88559