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Orexins Excite Neurons of the Rat Cerebellar Nucleus Interpositus Via Orexin 2 Receptors In Vitro

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Abstract

Orexins are newfound hypothalamic neuropeptides implicated in the regulation of feeding behavior, sleep–wakefulness cycle, nociception, addiction, emotions, as well as narcolepsy. However, little is known about roles of orexins in motor control. Therefore, the present study was designed to investigate the effect of orexins on neuronal activity in the cerebellum, an important subcortical center for motor control. In this study, perfusing slices with orexin A (100 nM–1 μM) or orexin B (100 nM–1 μM) both produced neurons in the rat cerebellar interpositus nucleus (IN) a concentration-dependent excitatory response (96/143, 67.1%). Furthermore, both of the excitations induced by orexin A and B were not blocked by the low-Ca2+/high-Mg2+ medium (n = 8), supporting a direct postsynaptic action of the peptides. Highly selective orexin 1 receptor antagonist SB-334867 did not block the excitatory response of cerebellar IN neurons to orexins (n = 22), but [Ala11, D-Leu15] orexin B, a highly selective orexin 2 receptor (OX2R) agonist, mimicked the excitatory effect of orexins on the cerebellar neurons (n = 18). These results demonstrate that orexins excite the cerebellar IN neurons through OX2R and suggest that the central orexinergic nervous system may actively participate in motor control through its modulation on one of the final outputs of the spinocerebellum.

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Acknowledgements

This work was supported by grants 30370462, 30670671, 30700201, and NSFC/RGC Joint Research Scheme 30910267 from the National Natural Science Foundation of China, RFDP grants 20050284025 and 20070284057 from the State Educational Ministry of China, and grant BK2006713 from the Natural Science Foundation of Jiangsu Province, China. The work was also partially supported by the 111 Project of the state Educational Ministry of China.

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  1. Department of Biological Science and Technology and State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Mailbox 426, Nanjing University, 22 Hankou Road, Nanjing, 210093, China

    Lei Yu, Xiao-Yang Zhang, Jun Zhang, Jing-Ning Zhu & Jian-Jun Wang

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Correspondence to Jing-Ning Zhu or Jian-Jun Wang.

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Yu, L., Zhang, XY., Zhang, J. et al. Orexins Excite Neurons of the Rat Cerebellar Nucleus Interpositus Via Orexin 2 Receptors In Vitro. Cerebellum 9, 88–95 (2010). https://doi.org/10.1007/s12311-009-0146-0

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