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

    Research output: Contribution to journalArticle

    62 Citations (Scopus)

    Abstract

    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
    Volume70
    Issue number6
    DOIs
    Publication statusPublished - 2002 Dec 15

    Fingerprint

    Calcium-Calmodulin-Dependent Protein Kinase Type 2
    Suprachiasmatic Nucleus
    Long-Term Potentiation
    Melatonin
    Cyclosporine
    Phospho-Specific Antibodies
    Hippocampal CA1 Region
    Synaptic Potentials
    Neuronal Plasticity
    Vasoactive Intestinal Peptide
    Glutamate Receptors
    Optic Nerve
    Mitogen-Activated Protein Kinases
    N-Methyl-D-Aspartate Receptors
    Immunoblotting
    Nitric Oxide Synthase
    Synaptic Transmission
    Carrier Proteins
    Therapeutics
    Immunohistochemistry

    Keywords

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

    ASJC Scopus subject areas

    • Neuroscience(all)

    Cite this

    Ca2+/calmodulin-dependent protein kinase II-dependent long-term potentiation in the rat suprachiasmatic nucleus and its inhibition by melatonin. / Fukunaga, Kohji; Horikawa, Kazumasa; Shibata, Shigenobu; Takeuchi, Yusuke; Miyamoto, Eishichi.

    In: Journal of Neuroscience Research, Vol. 70, No. 6, 15.12.2002, p. 799-807.

    Research output: Contribution to journalArticle

    @article{06df3683374b480d94c7d6860ccb7e9e,
    title = "Ca2+/calmodulin-dependent protein kinase II-dependent long-term potentiation in the rat suprachiasmatic nucleus and its inhibition by melatonin",
    abstract = "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.",
    keywords = "Calcineurin, CaM kinase II, Circadian rhythm, LTP, NOS, SCN",
    author = "Kohji Fukunaga and Kazumasa Horikawa and Shigenobu Shibata and Yusuke Takeuchi and Eishichi Miyamoto",
    year = "2002",
    month = "12",
    day = "15",
    doi = "10.1002/jnr.10400",
    language = "English",
    volume = "70",
    pages = "799--807",
    journal = "Journal of Neuroscience Research",
    issn = "0360-4012",
    publisher = "Wiley-Liss Inc.",
    number = "6",

    }

    TY - JOUR

    T1 - Ca2+/calmodulin-dependent protein kinase II-dependent long-term potentiation in the rat suprachiasmatic nucleus and its inhibition by melatonin

    AU - Fukunaga, Kohji

    AU - Horikawa, Kazumasa

    AU - Shibata, Shigenobu

    AU - Takeuchi, Yusuke

    AU - Miyamoto, Eishichi

    PY - 2002/12/15

    Y1 - 2002/12/15

    N2 - 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.

    AB - 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.

    KW - Calcineurin

    KW - CaM kinase II

    KW - Circadian rhythm

    KW - LTP

    KW - NOS

    KW - SCN

    UR - http://www.scopus.com/inward/record.url?scp=0037114677&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=0037114677&partnerID=8YFLogxK

    U2 - 10.1002/jnr.10400

    DO - 10.1002/jnr.10400

    M3 - Article

    VL - 70

    SP - 799

    EP - 807

    JO - Journal of Neuroscience Research

    JF - Journal of Neuroscience Research

    SN - 0360-4012

    IS - 6

    ER -