Abstract
The orexinergic system has a crucial role in regulation of wakefulness and a deficiency of orexinegic system causes narcolepsy. The orexinergic neurons project to and excite the brainstem aminergic and cholinergic neurons. So, the mechanisms of wakefulness regulation are well understood by these excitatory projections. However, current knowledge that orexins excite the cholinergic neurons does not explain the mechanisms of the suppression of cataplexy by the orexinergic system, because activation of the brainstem cholinergic neurons induces sudden reduction of muscular tonus (muscular atonia), equivalent to cataplexy. In decebrated cats, injection of orexin A into the muscular atonia inducing area (pedunculopontine tegmental nucleus; PPN) suppressed the cataplexic state. The effect was reversed by additional injections of bicuculline (GABAA antagonist) into the PPN. The similar effect of orexin was observed when injected into the substantia nigra pars reticulata (SNr), one of the origins of GABAergic input to the PPN, and was also reversed by bicuculline into the PPN. In freely moving rats, orexin injection into the PPN increased GABA release in the PPN which was measured by microdialysis-HPLC method. These findings suggest that the orexinergic system suppresses the atonia system by enhancement of GABAergic effects upon the cholinergic PPN neurons. In the absence of orexin, the attenuation of GABAergic excitability would result in cataplexy. [Jpn J Physiol 55 Suppl:S19 (2005)]
