演題番号 : O1-9-3-4
田淵 紗和子 / Sawako Tabuchi:1 常松 友美 / Tomomi Tsunematsu:1 富永 真琴 / Makoto Tominaga:1 深澤 有吾 / Yugo Fukazawa:1 山中 章弘 / Akihiro Yamanaka:1
1:生理学研究所・細胞生理 / Cell Signaling, NIPS, Aichi
Orexin is a neuropeptide which is produced in few number of neurons (orexin neurons) located in the lateral hypothalamic area. Orexin is a natural ligand for two types of G-protein coupled receptors termed OX1R and OX2R. Prepro-orexin or OX2R null animals showed a fragmentation of sleep/wakefulness and cataplexy-like behavioral arrest. These are similar to symptoms observed in "narcolepsy", a human sleep disorder. These suggest that orexin and OX2R have an important role in the maintenance of arousal. However, it is not clear that which neurons expressing the OX2R are involved. Electrophysiological analysis of orexin neurons using orexin/EGFP mice, which express EGFP in the orexin neurons, revealed that orexin activates orexin neurons in a concentration dependent manner. Orexin-induced depolarization was observed in the presence of TTX suggests direct activation. Additionally, orexin A and B induced equal level of depolarization suggests an involvement of the OX2R in this response. To determine the receptor subtype, orexin receptor knockout mice were used. Although orexin neurons in the OX1R-/- mice showed equal level of depolarization to orexin/EGFP mice, orexin neurons in the OX2R-/- mice did not show any significant depolarization by applying orexin. These results suggest that orexin activates orexin neurons via the OX2R. Next, we analyzed indirect regulation via glutamatergic neurons. sEPSC frequency to orexin neurons was increased by orexin application in the orexin/EGFP mice and OX1R-/- mice, but not in the OX2R-/- mice. On the other hand, immuno-electron microscopic analyses revealed synapse-like structures between orexin neurons, suggesting direct synaptic connection between orexin neurons. In conclusion, orexin activates orexin neurons directly and indirectly via the OX2R. An activation of orexin neurons by other orexin neurons via the OX2R might be involved in the maintenance of arousal.