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The lateral hypothalamus (LH) and zona incerta (ZI) regulate fear, but our understanding of the precise neural circuits and cell types involved remains limited. Here, we examined the role of relaxin family peptide receptor 3 (RXFP3) expressing cells in the LH\/ZI in conditioned fear expression and general arousal in male RXFP3\u2010Cre mice. We found that LH\/ZI RXFP3+ (LH\/ZI\n                    <jats:sup>RXFP3<\/jats:sup>\n                    ) cells projected strongly to fear learning, stress, and arousal centres, notably, the periaqueductal grey, lateral habenula, and nucleus reuniens. These cells do not express hypocretin\/orexin or melanin\u2010concentrating hormone but display putative efferent connectivity with LH hypocretin\/orexin+ neurons and dopaminergic A13 cells. Following Pavlovian fear conditioning, chemogenetically activating LH\/ZI\n                    <jats:sup>RXFP3<\/jats:sup>\n                    cells reduced fear expression (freezing) overall but also induced jumping behaviour and increased locomotor activity. Therefore, the decreased freezing was more likely to reflect enhanced arousal rather than reduced fear. Indeed, stimulating these cells produced distinct patterns of coactivation between several motor, stress, and arousal regions, as measured by Fos expression. These results suggest that activating LH\/ZI\n                    <jats:sup>RXFP3<\/jats:sup>\n                    cells generates brain\u2010wide activation patterns that augment behavioural arousal.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc16217-fig-0008-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.16217","type":"journal-article","created":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T00:52:46Z","timestamp":1725497566000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Relaxin family peptide receptor 3 (\n                    <scp>RXFP3<\/scp>\n                    ) expressing cells in the zona incerta\/lateral hypothalamus augment behavioural arousal"],"prefix":"10.1111","volume":"169","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4699-7585","authenticated-orcid":false,"given":"Brandon K.","family":"Richards","sequence":"first","affiliation":[{"name":"The Florey Institute of Neuroscience and Mental Health  Parkville Victoria Australia"},{"name":"Florey Department of Neuroscience and Mental Health The University of Melbourne  Parkville Victoria Australia"},{"name":"School of Psychological Sciences Macquarie University  North Ryde New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4927-796X","authenticated-orcid":false,"given":"Sarah S.","family":"Ch'ng","sequence":"additional","affiliation":[{"name":"The Florey Institute of Neuroscience and Mental Health  Parkville Victoria Australia"},{"name":"Florey Department of Neuroscience and Mental Health The University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariel B.","family":"Simon","sequence":"additional","affiliation":[{"name":"The Florey Institute of Neuroscience and Mental Health  Parkville Victoria Australia"},{"name":"Florey Department of Neuroscience and Mental Health The University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terence Y.","family":"Pang","sequence":"additional","affiliation":[{"name":"The Florey Institute of Neuroscience and Mental Health  Parkville Victoria Australia"},{"name":"Florey Department of Neuroscience and Mental Health The University of Melbourne  Parkville Victoria Australia"},{"name":"Institute of Health and Sports (IHES) Victoria University  Footscray Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jee 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