Orexins alleviate motor deficits via increasing firing activity of pallidal neurons in a mouse model of Parkinson's disease
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
References
Stimulation of glutamate receptors in the intermediate/caudal striatum induces contralateral turning
Progressive changes of orexin system in a rat model of 6-hydroxydopamine-induced Parkinson's disease
Citations
Apelin-13 regulates electrical activity in the globus pallidus and induces postural changes in rats.
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