Hypocretin-1 potentiates NMDA receptor-mediated somatodendritic secretion from locus ceruleus neurons

Xiao Wei Chen, Yu Mu, Hong Ping Huang, Ning Guo, Bo Zhang, Shuang Yi Fan, Jia Xiang Xiong, Shi Rong Wang, Wei Xiong, Wei Huang, Tao Liu, Liang Hong Zheng, Claire Xi Zhang, Li Huan Li, Zheng Ping Yu, Zhi An Hu*, Zhuan Zhou

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

Abstract

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 Ca 2+ 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.

Original languageEnglish
Pages (from-to)3202-3208
Number of pages7
JournalJournal of Neuroscience
Volume28
Issue number12
DOIs
Publication statusPublished - 19 Mar 2008
Externally publishedYes

Keywords

  • Amperometry
  • Hypocretin
  • Locus ceruleus
  • NMDA
  • Noradrenaline
  • Somatic secretion

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