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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:p>\n                    The locus coeruleus (LC) is a small nucleus in the pons from which ascending and descending projections innervate major parts of the central nervous system. Its major transmitter is norepinephrine (NE). This system is evolutionarily conserved, including in humans, and its functions are associated with wakefulness and related to disorders, such as depression. Here, we performed single-cell ribonucleic acid-sequencing (RNA-seq) to subdivide neurons in the LC (24 clusters in total) into 3 NE, 17 glutamate, and 5 \u03b3-aminobutyric acid (GABA) subtypes, and to chart their neuropeptide, cotransmitter, and receptor profiles. We found that NE neurons expressed at least 19 neuropeptide transcripts, notably galanin (\n                    <jats:italic>Gal<\/jats:italic>\n                    ) but not\n                    <jats:italic>Npy<\/jats:italic>\n                    , and &gt;30 neuropeptide receptors. Among the galanin receptors,\n                    <jats:italic>Galr1<\/jats:italic>\n                    was expressed in ~19% of NE neurons, as was also confirmed by in situ hybridization. Unexpectedly,\n                    <jats:italic>Galr1<\/jats:italic>\n                    was highly expressed in GABA neurons surrounding the NE ensemble. Patch-clamp electrophysiology and cell-type-specific Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -imaging using GCaMP6s revealed that a GalR1 agonist inhibits up to ~35% of NE neurons. This effect is direct and does not rely on feed-forward GABA inhibition. Our results define a role for the galanin system in NE functions, and a conceptual framework for the action of many other peptides and their receptors.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2222095120","type":"journal-article","created":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T15:08:10Z","timestamp":1690211290000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":39,"title":["Neuronal diversity of neuropeptide signaling, including galanin, in the mouse locus coeruleus"],"prefix":"10.1073","volume":"120","author":[{"given":"Martino","family":"Caramia","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Biomedicum, Karolinska Institutet, Stockholm 17177, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman A.","family":"Romanov","sequence":"additional","affiliation":[{"name":"Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, Vienna 1090, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spyridon","family":"Sideromenos","sequence":"additional","affiliation":[{"name":"Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, Vienna 1090, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsofia","family":"Hevesi","sequence":"additional","affiliation":[{"name":"Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, Vienna 1090, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Biomedicum, Karolinska Institutet, Stockholm 17177, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marharyta","family":"Krasniakova","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Biomedicum, Karolinska Institutet, Stockholm 17177, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Qing David","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Beijing Key Laboratory of Neural Regeneration and Repair, Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, China"},{"name":"Department of Pathology, Beijing Key Laboratory of Neural Regeneration and Repair, Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6637-5900","authenticated-orcid":false,"given":"Tibor","family":"Harkany","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Biomedicum, Karolinska Institutet, Stockholm 17177, Sweden"},{"name":"Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, Vienna 1090, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3587-0116","authenticated-orcid":false,"given":"Tomas G. 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