Ca2+/calmodulin-dependent protein kinase II-dependent long-term potentiation in the rat suprachiasmatic nucleus and its inhibition by melatonin

Kohji Fukunaga*, Kazumasa Horikawa, Shigenobu Shibata, Yusuke Takeuchi, Eishichi Miyamoto

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

69 Citations (Scopus)


We recently reported that Ca2+/calmodulin-dependent protein (CaM) kinase II is involved in light-induced phase delays and Per gene induction in the suprachiasmatic nucleus (SCN). To clarify the activation mechanisms of CaM kinase II by glutamate receptor stimulation in the SCN, we documented CaM kinase II activation following induction of long-term potentiation (LTP) in the rat SCN. High-frequency stimulation (100 Hz, 1 sec) applied to the optic nerve resulted in LTP of a postsynaptic field potential in the rat SCN. Unlike LTP in the hippocampal CA1 region, LTP onset in the SCN was slow and partly dependent on N-methyl-D-aspartate receptor activation. LTP induction in the SCN was completely inhibited by treatment with a nitric oxide synthase inhibitor or with a specific CaM kinase II inhibitor. Immunoblotting analysis using phosphospecific antibodies against autophosphorylated CaM kinase II revealed that LTP induction was accompanied by an increase in autophosphorylation. After high-frequency stimulation, we could visualize activation of CaM kinase II in vasoactive intestinal polypeptide-positive neurons in the SCN by immunohistochemistry. Treatment with cyclosporin A, a calcineurin inhibitor, potentiated LTP induction in the rat SCN. Interestingly, treatment with melatonin totally prevented LTP induction, without changes in basal synaptic transmission. Analyses of phosphorylation of CaM kinase II, mitogen-activated protein kinase, and cAMP-responsive element binding protein revealed that stimulatory and inhibitory effects on CaM kinase II autophosphorylation underlie the effects of cyclosporin A and melatonin, respectively. These results suggest that CaM kinase II plays critical roles in LTP induction in the SCN and that melatonin has inhibitory effects on synaptic plasticity through CaM kinase II.

Original languageEnglish
Pages (from-to)799-807
Number of pages9
JournalJournal of Neuroscience Research
Issue number6
Publication statusPublished - 2002 Dec 15


  • CaM kinase II
  • Calcineurin
  • Circadian rhythm
  • LTP
  • NOS
  • SCN

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience


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