Glutamate regulates the frequency of spontaneous synchronized Ca2+ spikes through group II metabotropic glutamate receptor in cultured mouse cortical networks
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作者:
Yasumoto, F
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机构:Univ Tokyo, Grad Sch Agr & Life Sci, Dept Biomed Sci, Bunkyo Ku, Tokyo 1138657, Japan
Yasumoto, F
Negishi, T
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机构:Univ Tokyo, Grad Sch Agr & Life Sci, Dept Biomed Sci, Bunkyo Ku, Tokyo 1138657, Japan
Negishi, T
Ishii, Y
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机构:Univ Tokyo, Grad Sch Agr & Life Sci, Dept Biomed Sci, Bunkyo Ku, Tokyo 1138657, Japan
Ishii, Y
Kyuwa, S
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机构:Univ Tokyo, Grad Sch Agr & Life Sci, Dept Biomed Sci, Bunkyo Ku, Tokyo 1138657, Japan
Kyuwa, S
Kuroda, Y
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机构:Univ Tokyo, Grad Sch Agr & Life Sci, Dept Biomed Sci, Bunkyo Ku, Tokyo 1138657, Japan
Kuroda, Y
Yoshikawa, Y
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机构:Univ Tokyo, Grad Sch Agr & Life Sci, Dept Biomed Sci, Bunkyo Ku, Tokyo 1138657, Japan
Yoshikawa, Y
机构:
[1] Univ Tokyo, Grad Sch Agr & Life Sci, Dept Biomed Sci, Bunkyo Ku, Tokyo 1138657, Japan
[2] Tokyo Metropolitan Inst Neurosci, Dept Mol & Cellular Neurobiol, Fuchu, Tokyo, Japan
[3] Japan Sci & Technol Corp, Core Res Evolut Sci & Technol, Kawaguchi, Saitama, Japan
1. Synchronized spontaneous intracellular Ca2+ spikes in networked neurons are believed to play a major role in the development and plasticity of neural circuits. Glutamate-induced signals through the ionotropic glutamate receptors (iGluRs) are profoundly involved in the generation of synchronized Ca2+ spikes. 2. In this study, we examined the involvement of metabotropic glutamate receptors (mGluRs) in cultured mouse cortical neurons. We pharmacologically revealed that glutamate-induced signals through inclusive mGluRs decreased the frequency of Ca2+ spikes. Further experiments indicated that this suppressive effect on the spike frequency was mainly due to the signal through group II mGluR, inactivation of adenylate cyclase-cAMP-PKA signaling pathway. Group I mGluR had little involvement in the spike frequency. 3. Taken together, glutamate generates the synchronized Ca2+ spikes through iGluRs and modulates simultaneously their frequency through group II mGluR-adenylate cyclase-cAMP-PKA signaling pathway in the present in vitro neural network. These results provide the evidence of the profound role of group II mGluR in the spontaneous and synchronous neural activities.