Laboratory of Molecular and Behavioral Neuroscience, Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland; Neuroscience Center Zurich, ETH Zurich and University of Zurich, Switzerland, Zurich, Switzerland
Lukas M von Ziegler
Laboratory of Molecular and Behavioral Neuroscience, Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland; Neuroscience Center Zurich, ETH Zurich and University of Zurich, Switzerland, Zurich, Switzerland
Laboratory of Molecular and Behavioral Neuroscience, Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland; Neuroscience Center Zurich, ETH Zurich and University of Zurich, Switzerland, Zurich, Switzerland
Laboratory of Molecular and Behavioral Neuroscience, Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland; Neuroscience Center Zurich, ETH Zurich and University of Zurich, Switzerland, Zurich, Switzerland
Laboratory of Molecular and Behavioral Neuroscience, Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland
Laboratory of Molecular and Behavioral Neuroscience, Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland; Neuroscience Center Zurich, ETH Zurich and University of Zurich, Switzerland, Zurich, Switzerland
Sebastian Leimbacher
Laboratory of Molecular and Behavioral Neuroscience, Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland
Laboratory of Molecular and Behavioral Neuroscience, Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland; Neuroscience Center Zurich, ETH Zurich and University of Zurich, Switzerland, Zurich, Switzerland
Laboratory of Molecular and Behavioral Neuroscience, Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland
Laboratory of Neurochemistry and Behavior, Experimental Neurobiology Unit, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Division of Human Nutrition and Health, Chair Group of Nutritional Biology, Wageningen University & Research (WUR), Wageningen, Netherlands
Laboratory of Neurochemistry and Behavior, Experimental Neurobiology Unit, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Department of Neurology and Alzheimer Center, University of Groningen and University Medical Center Groningen (UMCG), Groningen, Netherlands
Laboratory of Neurochemistry and Behavior, Experimental Neurobiology Unit, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Department of Neurology and Alzheimer Center, University of Groningen and University Medical Center Groningen (UMCG), Groningen, Netherlands; Department of Neurology, Memory Clinic of Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium
Laboratory of Molecular and Behavioral Neuroscience, Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland; Neuroscience Center Zurich, ETH Zurich and University of Zurich, Switzerland, Zurich, Switzerland; Computational Neurogenomics, Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zürich, Zurich, Switzerland; Laboratory of Statistical Bioinformatics, University of Zürich, Zürich, Switzerland
Laboratory of Molecular and Behavioral Neuroscience, Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland; Neuroscience Center Zurich, ETH Zurich and University of Zurich, Switzerland, Zurich, Switzerland
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 β-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.
