期刊论文详细信息
eLife
Dissociating orexin-dependent and -independent functions of orexin neurons using novel Orexin-Flp knock-in mice
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[1] Department of Animal Model development, Brain Research Institute, Niigata University, Niigata, Japan;Department of Neurochemistry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan;Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan;Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan;Department of Neural Regulation, Graduate School of Medicine, Nagoya University, Nagoya, Japan;CREST, JST, Honcho Kawaguchi, Saitama, Japan;Research Center for Dynamic Living Systems, Graduate School of Biostudies, Kyoto University, Kyoto, Japan;
关键词: orexin/hypocretin;    flippase recombinase;    electrophysiology;    chemogenetics;    sleep/wakefulness;    cataplexy;    Mouse;   
DOI  :  10.7554/eLife.44927
来源: publisher
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【 摘 要 】

10.7554/eLife.44927.001Uninterrupted arousal is important for survival during threatening situations. Activation of orexin/hypocretin neurons is implicated in sustained arousal. However, orexin neurons produce and release orexin as well as several co-transmitters including dynorphin and glutamate. To disambiguate orexin-dependent and -independent physiological functions of orexin neurons, we generated a novel Orexin-flippase (Flp) knock-in mouse line. Crossing with Flp-reporter or Cre-expressing mice showed gene expression exclusively in orexin neurons. Histological studies confirmed that orexin was knock-out in homozygous mice. Orexin neurons without orexin showed altered electrophysiological properties, as well as received decreased glutamatergic inputs. Selective chemogenetic activation revealed that both orexin and co-transmitters functioned to increase wakefulness, however, orexin was indispensable to promote sustained arousal. Surprisingly, such activation increased the total time spent in cataplexy. Taken together, orexin is essential to maintain basic membrane properties and input-output computation of orexin neurons, as well as to exert awake-sustaining aptitude of orexin neurons.

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