上皮成長因子受容体活性化による皮質GABA作働性神経シナプス発達の低下 EGF receptor (ErbB1) stimulation down-regulates synaptic inputs of neocortical GABAergic neurons

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Author(s)

    • 難波 寿明 Namba Hisaaki
    • 新潟大学・脳研・分子神経生物 Dept. of Mol. Neurobiol., Brain Res. Inst., Niigata Univ., Niigata, Japan
    • 永野 忠望 Nagano Tadasato
    • 新潟大学・脳研・分子神経生物|金沢大学医学系研究科脳情報回路学講座 Dept. of Mol. Neurobiol., Brain Res. Inst., Niigata Univ., Niigata, Japan|Dept. of Cell. Neurophysiol., Grad. Sch. of Med. Sci., Kanazawa Univ., Kanazawa, Japan
    • 鄭 英君 Zheng Yingjun
    • 新潟大学・脳研・分子神経生物 Dept. of Mol. Neurobiol., Brain Res. Inst., Niigata Univ., Niigata, Japan
    • 那波 宏之 Nawa Hiroyuki
    • 新潟大学・脳研・分子神経生物 Dept. of Mol. Neurobiol., Brain Res. Inst., Niigata Univ., Niigata, Japan

Abstract

Neurotrophins and cytokines are involved in neuronal differentiation, synaptic development and plasticity. In neocortical culture, we reported epidermal growth factor (EGF) family (ErbB1 ligands; EGF, TGF-alpha, HB-EGF) down-regulates an AMPA receptor molecule, GluR1. Using neocortical cultures and EGF-administered animals, we electrophysiologically evaluated the effects of the EGF family on synaptic development and plasticity in the GABAergic neurons. In neocortical culture, subchronic treatment with TGF-alpha reduced the expression of GluR1-immunoreactivity in glutamic acid decarboxylase (GAD) 67 immunopositive GABAergic neurons. Whole-cell patch-clamp recording from morphologically identified putative GABAergic neurons revealed decreases both in AMPA currents and amplitudes of mEPSCs by TGF-alpha. Subcutaneous administration of EGF for 14 days in neonatal mice also decreased protein levels of AMPA and NMDA receptors in the frontal cortex. Immunohistochemical study revealed that the decrease in GluR1 levels was relatively specific for the parvalbumin-positive GABAergic neurons. Miniature analyses in cortical slices show that the amplitudes of mEPSCs in the GABAergic neurons decreased significantly, whereas no alteration was observed in the pyramidal neurons. Thus, activation of ErbB1 receptors during cortical development negatively regulates synaptic inputs and plasticity in the GABAergic neurons. <b>[J Physiol Sci. 2006;56 Suppl:S171]</b>

Neurotrophins and cytokines are involved in neuronal differentiation, synaptic development and plasticity. In neocortical culture, we reported epidermal growth factor (EGF) family (ErbB1 ligands; EGF, TGF-alpha, HB-EGF) down-regulates an AMPA receptor molecule, GluR1. Using neocortical cultures and EGF-administered animals, we electrophysiologically evaluated the effects of the EGF family on synaptic development and plasticity in the GABAergic neurons. In neocortical culture, subchronic treatment with TGF-alpha reduced the expression of GluR1-immunoreactivity in glutamic acid decarboxylase (GAD) 67 immunopositive GABAergic neurons. Whole-cell patch-clamp recording from morphologically identified putative GABAergic neurons revealed decreases both in AMPA currents and amplitudes of mEPSCs by TGF-alpha. Subcutaneous administration of EGF for 14 days in neonatal mice also decreased protein levels of AMPA and NMDA receptors in the frontal cortex. Immunohistochemical study revealed that the decrease in GluR1 levels was relatively specific for the parvalbumin-positive GABAergic neurons. Miniature analyses in cortical slices show that the amplitudes of mEPSCs in the GABAergic neurons decreased significantly, whereas no alteration was observed in the pyramidal neurons. Thus, activation of ErbB1 receptors during cortical development negatively regulates synaptic inputs and plasticity in the GABAergic neurons. <b>[J Physiol Sci. 2006;56 Suppl:S171]</b>

Journal

  • Proceedings of Annual Meeting of the Physiological Society of Japan

    Proceedings of Annual Meeting of the Physiological Society of Japan 2006(0), 171-171, 2006

    PHYSIOLOGICAL SOCIETY OF JAPAN

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