Noradrenaline release from the locus coeruleus shapes stress-induced hippocampal gene expression
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 man...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2024-03-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/88559 |
| _version_ | 1827318965139931136 |
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| author | Mattia Privitera Lukas M von Ziegler Amalia Floriou-Servou Sian N Duss Runzhong Zhang Rebecca Waag Sebastian Leimbacher Oliver Sturman Fabienne K Roessler Annelies Heylen Yannick Vermeiren Debby Van Dam Peter P De Deyn Pierre-Luc Germain Johannes Bohacek |
| author_facet | Mattia Privitera Lukas M von Ziegler Amalia Floriou-Servou Sian N Duss Runzhong Zhang Rebecca Waag Sebastian Leimbacher Oliver Sturman Fabienne K Roessler Annelies Heylen Yannick Vermeiren Debby Van Dam Peter P De Deyn Pierre-Luc Germain Johannes Bohacek |
| author_sort | Mattia Privitera |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-25T00:11:45Z |
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| id | doaj.art-e31eb3ec28a24c24ac3e22f507e84dfa |
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| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-25T00:11:45Z |
| publishDate | 2024-03-01 |
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| series | eLife |
| spelling | doaj.art-e31eb3ec28a24c24ac3e22f507e84dfa2024-03-13T13:03:15ZengeLife Sciences Publications LtdeLife2050-084X2024-03-011210.7554/eLife.88559Noradrenaline release from the locus coeruleus shapes stress-induced hippocampal gene expressionMattia Privitera0https://orcid.org/0000-0002-5660-5901Lukas M von Ziegler1Amalia Floriou-Servou2https://orcid.org/0000-0002-5090-4900Sian N Duss3https://orcid.org/0000-0003-0212-0324Runzhong Zhang4https://orcid.org/0000-0001-6144-5546Rebecca Waag5https://orcid.org/0000-0001-5103-2860Sebastian Leimbacher6Oliver Sturman7https://orcid.org/0000-0001-6859-4800Fabienne K Roessler8https://orcid.org/0000-0001-6594-1504Annelies Heylen9https://orcid.org/0000-0002-2660-8984Yannick Vermeiren10https://orcid.org/0000-0002-2091-5326Debby Van Dam11https://orcid.org/0000-0003-4739-6076Peter P De Deyn12https://orcid.org/0000-0002-2228-2964Pierre-Luc Germain13https://orcid.org/0000-0003-3418-4218Johannes Bohacek14https://orcid.org/0000-0002-8442-653XLaboratory 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, SwitzerlandLaboratory 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, SwitzerlandLaboratory 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, SwitzerlandLaboratory 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, SwitzerlandLaboratory of Molecular and Behavioral Neuroscience, Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, SwitzerlandLaboratory 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, SwitzerlandLaboratory of Molecular and Behavioral Neuroscience, Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, SwitzerlandLaboratory 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, SwitzerlandLaboratory of Molecular and Behavioral Neuroscience, Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, SwitzerlandLaboratory of Neurochemistry and Behavior, Experimental Neurobiology Unit, Department of Biomedical Sciences, University of Antwerp, Antwerp, BelgiumLaboratory 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, NetherlandsLaboratory 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, NetherlandsLaboratory 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, BelgiumLaboratory 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, SwitzerlandLaboratory 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, SwitzerlandExposure 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.https://elifesciences.org/articles/88559transcriptomenoradrenalinelocus coeruleushippocampusstressoptogenetics |
| spellingShingle | Mattia Privitera Lukas M von Ziegler Amalia Floriou-Servou Sian N Duss Runzhong Zhang Rebecca Waag Sebastian Leimbacher Oliver Sturman Fabienne K Roessler Annelies Heylen Yannick Vermeiren Debby Van Dam Peter P De Deyn Pierre-Luc Germain Johannes Bohacek Noradrenaline release from the locus coeruleus shapes stress-induced hippocampal gene expression eLife transcriptome noradrenaline locus coeruleus hippocampus stress optogenetics |
| title | Noradrenaline release from the locus coeruleus shapes stress-induced hippocampal gene expression |
| title_full | Noradrenaline release from the locus coeruleus shapes stress-induced hippocampal gene expression |
| title_fullStr | Noradrenaline release from the locus coeruleus shapes stress-induced hippocampal gene expression |
| title_full_unstemmed | Noradrenaline release from the locus coeruleus shapes stress-induced hippocampal gene expression |
| title_short | Noradrenaline release from the locus coeruleus shapes stress-induced hippocampal gene expression |
| title_sort | noradrenaline release from the locus coeruleus shapes stress induced hippocampal gene expression |
| topic | transcriptome noradrenaline locus coeruleus hippocampus stress optogenetics |
| url | https://elifesciences.org/articles/88559 |
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