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Inflammatory signaling in the hypothalamus mediates the febrile and anorectic responses to disease, but the mechanism by which locomotor activity (LMA) is suppressed has not been described. Lateral hypothalamic orexin (Ox) neurons link energy status with LMA, and deficiencies in Ox signaling lead to hypoactivity and hypophagia. In the present work, we examine the effect of endotoxin-induced inflammation on Ox neuron biology and LMA in rats. Our results demonstrate a vital role for diminished Ox signaling in mediating inflammation-induced lethargy. This work defines a specific population of inflammation-sensitive, arousal-associated Ox neurons and identifies a proximal neural target for inflammatory signaling to Ox neurons, while eliminating several others.<\/jats:p>","DOI":"10.1523\/jneurosci.2311-11.2011","type":"journal-article","created":{"date-parts":[[2011,8,3]],"date-time":"2011-08-03T23:48:44Z","timestamp":1312415324000},"page":"11376-11386","source":"Crossref","is-referenced-by-count":123,"title":["Inflammation-Induced Lethargy Is Mediated by Suppression of Orexin Neuron Activity"],"prefix":"10.1523","volume":"31","author":[{"given":"Aaron J.","family":"Grossberg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"XinXia","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gina M.","family":"Leinninger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter R.","family":"Levasseur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore P.","family":"Braun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Martin G.","family":"Myers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel L.","family":"Marks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2011,8,3]]},"reference":[{"key":"2023041303514767000_31.31.11376.1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2009-0865"},{"key":"2023041303514767000_31.31.11376.2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.19.14563"},{"key":"2023041303514767000_31.31.11376.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2007.06.002"},{"key":"2023041303514767000_31.31.11376.4","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81973-X"},{"key":"2023041303514767000_31.31.11376.5","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(91)91587-Q"},{"key":"2023041303514767000_31.31.11376.6","doi-asserted-by":"publisher","DOI":"10.1210\/en.143.3.755"},{"key":"2023041303514767000_31.31.11376.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2007.05.003"},{"key":"2023041303514767000_31.31.11376.8","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1111\/j.1749-6632.2001.tb05827.x","article-title":"Cytokine-induced sickness behavior: mechanisms and implications","volume":"933","author":"Dantzer","year":"2001","journal-title":"Ann N Y Acad Sci"},{"key":"2023041303514767000_31.31.11376.9","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1093\/sleep\/27.5.851","article-title":"The diurnal rhythm of hypocretin in young and old F344 rats","volume":"27","author":"Desarnaud","year":"2004","journal-title":"Sleep"},{"key":"2023041303514767000_31.31.11376.10","doi-asserted-by":"publisher","DOI":"10.1038\/nn1137"},{"key":"2023041303514767000_31.31.11376.11","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1523\/JNEUROSCI.21-05-01656.2001","article-title":"Fos expression in orexin neurons varies with behavioral state","volume":"21","author":"Estabrooke","year":"2001","journal-title":"J Neurosci"},{"key":"2023041303514767000_31.31.11376.12","doi-asserted-by":"publisher","DOI":"10.1007\/s002130050353"},{"key":"2023041303514767000_31.31.11376.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2009.03.005"},{"key":"2023041303514767000_31.31.11376.14","doi-asserted-by":"crossref","first-page":"3106","DOI":"10.1523\/JNEUROSCI.23-08-03106.2003","article-title":"Involvement of the lateral hypothalamic peptide orexin in morphine dependence and withdrawal","volume":"23","author":"Georgescu","year":"2003","journal-title":"J Neurosci"},{"key":"2023041303514767000_31.31.11376.15","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(80)90123-7"},{"key":"2023041303514767000_31.31.11376.16","doi-asserted-by":"publisher","DOI":"10.1210\/en.2009-1135"},{"key":"2023041303514767000_31.31.11376.17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.19.10911"},{"key":"2023041303514767000_31.31.11376.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2006.08.002"},{"key":"2023041303514767000_31.31.11376.19","doi-asserted-by":"publisher","DOI":"10.1016\/S0196-9781(99)00105-9"},{"key":"2023041303514767000_31.31.11376.20","doi-asserted-by":"publisher","DOI":"10.1172\/JCI46229"},{"key":"2023041303514767000_31.31.11376.21","doi-asserted-by":"crossref","unstructured":"Leinninger GM Opland DM Jo Y-H Faouzi M Gong Y Christensen L Cappellucci L Pothos E Yang H Becker JB Thompson RC Seasholtz AF Gnegy ME Myers MG (2011) Lateral hypothalamic leptin receptor neurons containing neurotensin regulate orexin neurons, energy balance and the mesolimbic dopamine system. 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