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All noradrenergic signalling provided by this nucleus is dependent on an intrinsic pacemaker process. Our study aims to understand how noradrenergic neurons finely tune their pacemaker processes and regulate their activities. Here we present that mitochondrial perturbation in the <jats:styled-content style=\"fixed-case\">LC<\/jats:styled-content> from mice, inhibits spontaneous firing by a hyperpolarizing response that involves Ca<jats:sup>2+<\/jats:sup> entry via L\u2010type Ca<jats:sup>2+<\/jats:sup> channels and the actin cytoskeleton. We found that pharmacological perturbation of mitochondria from <jats:styled-content style=\"fixed-case\">LC<\/jats:styled-content> neurons using the protonophore carbonyl cyanide m\u2010chlorophenylhydrazone (<jats:styled-content style=\"fixed-case\">CCCP<\/jats:styled-content>), induced a dominant hyperpolarizing response when electrophysiological approaches were performed. Surprisingly, the <jats:styled-content style=\"fixed-case\">CCCP<\/jats:styled-content>\u2010induced hyperpolarizing response was dependent on L\u2010type Ca<jats:sup>2+<\/jats:sup> channel\u2010mediated Ca<jats:sup>2+<\/jats:sup> entry, as it was inhibited by: the removal of extracellular Ca<jats:sup>2+<\/jats:sup>; the addition of Cd<jats:sup>2+<\/jats:sup>; nifedipine or nicardipine; but not by the intracellular dialysis with the Ca<jats:sup>2+<\/jats:sup> chelator 1,2\u2010Bis(2\u2010Aminophenoxy)ethane\u2010N,N,N\u2032,N\u2032\u2010tetraacetic acid, the latter indicating that the response was not because of a global change in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>c<\/jats:sub> but does not exclude action at intracellular microdomains. Further to this, the incubation of slices with cytochalasin D, an agent that depolymerises the actin cytoskeleton, inhibited the hyperpolarizing response indicating an involvement of the actin cytoskeleton. The data are consistent with the hypothesis that there is a crosstalk between mitochondria and L\u2010type Ca<jats:sup>2+<\/jats:sup> channels leading to modulation of noradrenergic neuronal activity mediated by the actin cytoskeleton.<\/jats:p><\/jats:sec><jats:sec><jats:title>Open Science Badges<\/jats:title><jats:p><jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/jnc14692-gra-0001.png\" xlink:title=\"image\"\/><\/jats:p><jats:p>This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/cos.io\/our-services\/open-science-badges\/\">https:\/\/cos.io\/our-services\/open-science-badges\/<\/jats:ext-link>.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc14692-fig-0011-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.14692","type":"journal-article","created":{"date-parts":[[2019,3,4]],"date-time":"2019-03-04T07:04:40Z","timestamp":1551683080000},"page":"471-487","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Crosstalk between mitochondria, calcium channels and actin cytoskeleton modulates noradrenergic activity of locus coeruleus neurons"],"prefix":"10.1111","volume":"149","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0431-2725","authenticated-orcid":false,"given":"Ramatis B.","family":"de Oliveira","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy University of Newcastle and Hunter Medical Research Institute Callaghan NSW Australia"},{"name":"Health and Medical Research Group School of Medicine University of the Taquari Valley \u2010 Univates Lajeado RS Brazil"},{"name":"Bairro Universit\u00e1rio Lajeado RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4258-2649","authenticated-orcid":false,"given":"Lyvia L.","family":"Petiz","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy University of Newcastle and Hunter Medical Research Institute Callaghan NSW Australia"},{"name":"Brain 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