TY - JOUR T1 - Hypocretin-1 Potentiates NMDA Receptor-Mediated Somatodendritic Secretion from Locus Ceruleus Neurons JF - The Journal of Neuroscience JO - J. Neurosci. SP - 3202 LP - 3208 DO - 10.1523/JNEUROSCI.4426-07.2008 VL - 28 IS - 12 AU - Xiao-Wei Chen AU - Yu Mu AU - Hong-Ping Huang AU - Ning Guo AU - Bo Zhang AU - Shuang-Yi Fan AU - Jia-Xiang Xiong AU - Shi-Rong Wang AU - Wei Xiong AU - Wei Huang AU - Tao Liu AU - Liang-Hong Zheng AU - Claire Xi Zhang AU - Li-Huan Li AU - Zheng-Ping Yu AU - Zhi-An Hu AU - Zhuan Zhou Y1 - 2008/03/19 UR - http://www.jneurosci.org/content/28/12/3202.abstract N2 - Our previous observations showed that several stimuli, including high-K+ solution, glutamate, and voltage pulses, induce somatic noradrenaline (NA) secretion from locus ceruleus (LC) neurons. Hypocretin (orexin), a hypothalamic peptide critical for normal wakefulness, has been shown to evoke NA release from the axon terminals of LC neurons. Here, we used amperometry to test the effect of hypocretin-1 (HCRT) on NMDA receptor-mediated somatodendritic release in LC neurons. Either HCRT or NMDA applied alone dose-dependently induced somatodendritic secretion. Bath application of HCRT notably potentiated NMDA receptor-mediated somatodendritic NA release. This potentiation was blocked by SB 334867, a selective HCRT receptor (Hcrtr 1) antagonist, or bisindolylmaleimide, a specific protein kinase C (PKC) inhibitor, indicating the involvement of Hcrtr 1 and PKC. Consistent with this, phorbol 12-myristate 13-acetate, a PKC activator, mimicked the HCRT-induced potentiation. Furthermore, HCRT enhanced NMDA-induced intracellular Ca2+ elevation via activation of Hcrtr 1 and PKC, which may contribute to HCRT-potentiated somatodendritic secretion. These results suggest that HCRT modulates LC activity not only by regulating noradrenergic input to its targets, but also by affecting noradrenergic communication in the soma and dendrites. ER -