Abstract：
:Hypocretin-1 and -2 (Hcrt-1 and -2, also called orexin-A and -B) are newly identified neuropeptides synthesized by hypothalamic neurons. Defects in the Hcrt system underlie the sleep disorder narcolepsy, which is characterized by sleep fragmentation and the involuntary loss of muscle tone called cataplexy. Hcrt neurons project to multiple brain regions including cranial and spinal motor nuclei. In vitro studies suggest that Hcrt application can modulate presynaptic glutamate release. Together these observations suggest that Hcrt can affect motor output and that glutamatergic processes may be involved. We addressed these issues in decerebrate cats by applying Hcrt-1 and -2 into the trigeminal motor nucleus to determine whether these ligands alter masseter muscle activity and by pretreating the trigeminal motor nucleus with a N-methyl-d-aspartate (NMDA) antagonist to determine if glutamatergic pathways are involved in the transduction of the Hcrt signal. We found that Hcrt-1 and -2 microinjections into the trigeminal motor nucleus increased ipsilateral masseter muscle tone in a dose-dependent manner. We also found that Hcrt application into the hypoglossal motor nucleus increases genioglossus muscle activity. Pretreatment with a NMDA antagonist (d-(-)-2-amino-phosphonovaleric acid) abolished the excitatory response of the masseter muscle to Hcrt-1 application; however, pretreatment with methysergide, a serotonin antagonist had no effect. These studies are the first to demonstrate that Hcrt causes the excitation of motoneurons and that functional NMDA receptors are required for this response. We suggest that Hcrt regulates motor control processes and that this regulation is mediated by glutamate release in the trigeminal motor nucleus.
journal_name
J Neurophysioljournal_title
Journal of neurophysiologyauthors
Peever JH,Lai YY,Siegel JMdoi
10.1152/jn.00968.2002subject
Has Abstractpub_date
2003-05-01 00:00:00pages
2591-600issue
5eissn
0022-3077issn
1522-1598pii
00968.2002journal_volume
89pub_type
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