Inflammation-induced lethargy is mediated by suppression of orexin neuron activity

Aaron J. Grossberg, Xinxia Zhu, Gina M. Leinninger, Peter R. Levasseur, Theodore P. Braun, Martin G. Myers, Daniel L. Marks

Research output: Contribution to journalArticlepeer-review

94 Scopus citations


In response to illness, animals subvert normal homeostasis and divert their energy utilization to fight infection. An important and unexplored feature of this response is the suppression of physical activity and foraging behavior in the setting of negative energy balance. 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.

Original languageEnglish (US)
Pages (from-to)11376-11386
Number of pages11
JournalJournal of Neuroscience
Issue number31
StatePublished - Aug 3 2011

ASJC Scopus subject areas

  • Neuroscience(all)


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