Orexins alleviate motor deficits via increasing firing activity of pallidal neurons in a mouse model of Parkinson's disease

American Journal of Physiology. Cell Physiology
Ying WangLei Chen

Abstract

Orexin is a peptide neurotransmitter released in the globus pallidus. Morphological evidence reveals that both orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R) exist in the globus pallidus. Here we showed that bilateral microinjection of both orexin-A and orexin-B into the globus pallidus alleviated motor deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonian mice. Further in vivo extracellular single-unit recording revealed that the basal spontaneous firing rate of the globus pallidus neurons in MPTP parkinsonian mice was slower than that of normal mice. Application of orexin-A or orexin-B significantly increased the spontaneous firing rate of pallidal neurons. The influx of Ca2+ through the L-type Ca2+ channel is the major mechanism involved in orexin-induced excitation in the globus pallidus. Orexin-A-induced increase in firing rate of pallidal neurons in MPTP parkinsonian mice was stronger than that of normal mice. Orexin-A exerted both electrophysiological and behavioral effects mainly via OX1R, and orexin-B exerted the effects via OX2R. Endogenous orexins modulated the excitability of globus pallidus neurons mainly through OX1R. The present behavioral and electrophysiological results sug...Continue Reading

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Feb 8, 2020·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Feifei MuHong Jiang

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