Abstract
Orexin deficiency results in cataplexy, a motor deficit characterized by sudden loss of muscle tone, strongly indicating an active role of central orexinergic system in motor control. However, effects of orexin on neurons in central motor structures are still largely unknown. Our previous studies have revealed that orexin excites neurons in the cerebellar nuclei and lateral vestibular nucleus, two important subcortical motor centers for control of muscle tone. Here, we report that both orexin-A and orexin-B depolarizes and increases the firing rate of neurons in the inferior vestibular nucleus (IVN), the largest nucleus in the vestibular nuclear complex and holding an important position in integration of information signals in the control of body posture. TTX does not block orexin-induced excitation on IVN neurons, suggesting a direct postsynaptic action of the neuropeptide. Furthermore, bath application of orexin induces an inward current on IVN neurons in a concentration-dependent manner. SB334867 and TCS-OX2-29, specific OX1 and OX2 receptor antagonists, blocked the excitatory effect of orexin, and [Ala11, D-Leu15]-orexin B, a selective OX2 receptor agonist, mimics the orexin-induced inward current on IVN neurons. qPCR and immunofluorescence results show that both OX1 and OX2 receptor mRNAs and proteins are expressed and localized in the rat IVN. These results demonstrate that orexin excites the IVN neurons by co-activation of both OX1 and OX2 receptors, suggesting that via the direct modulation on the IVN, the central orexinergic system may actively participate in the central vestibular-mediated postural and motor control.
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Acknowledgments
The work was supported by grants 31171050, 31330033, 91332124 and 31471112 from the National Natural Science Foundation of China; RFDP grant 20100091110016, SRFDP/RGC ERG grant 20130091140003 and NCET Program from the State Educational Ministry of China; grants BK2011014 and BK20140599 from the Natural Science Foundation of Jiangsu Province, China; grants 2013T60520 and 2014M550283 from the China Postdoctoral Science Foundation; grants 1202004C and 1302006C from the Jiangsu Planned Projects for Postdoctoral Research Funds.
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Yu, L., Zhang, XY., Chen, ZP. et al. Orexin excites rat inferior vestibular nuclear neurons via co-activation of OX1 and OX2 receptors. J Neural Transm 122, 747–755 (2015). https://doi.org/10.1007/s00702-014-1330-z
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DOI: https://doi.org/10.1007/s00702-014-1330-z