RT Journal Article
SR Electronic
T1 Orexin Directly Excites Orexin Neurons through Orexin 2 Receptor
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 12642
OP 12652
DO 10.1523/JNEUROSCI.2120-10.2010
VO 30
IS 38
A1 Yamanaka, Akihiro
A1 Tabuchi, Sawako
A1 Tsunematsu, Tomomi
A1 Fukazawa, Yugo
A1 Tominaga, Makoto
YR 2010
UL http://www.jneurosci.org/content/30/38/12642.abstract
AB Orexin neurons (hypocretin neurons) have a critical role in the regulation of sleep/wakefulness, especially in the maintenance of arousal. Here, we revealed that orexin neurons are directly and indirectly activated by orexin via the orexin 2 receptor (OX2R). Orexin B (1 μm) induced depolarization in orexin neurons, which was still observed in the presence of TTX (1 μm), AP-5 (50 μm), and CNQX (20 μm). In addition, orexin B induced inward currents in the presence of TTX, suggesting a direct activation of orexin neurons. Although orexin B application induced depolarization in orexin neurons of OX1R knock-out mice at comparable levels to wild-type mice, the observation that orexin B failed to depolarize orexin neurons in the OX2R knock-out mice suggested that OX2R was a primary receptor for this response. Moreover, immunoelectron microscopic analyses revealed direct contacts among orexin neurons, which exhibited structural similarities to the glutamatergic synapses. Together, these results suggest that orexin neurons form a positive-feedback circuit through indirect and direct pathways, which results in the preservation of the orexin neuron network at a high activity level and/or for a longer period. Therefore, the activation of orexin neurons through OX2R might have an important role in the maintenance of arousal.