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. 2004 Dec;24(6):841–852. doi: 10.1007/s10571-004-6923-x

Glutamate Regulates the Frequency of Spontaneous Synchronized Ca2+ Spikes Through Group II Metabotropic Glutamate Receptor in Cultured Mouse Cortical Networks

Fumie Yasumoto 1,3,✉, Takayuki Negishi 1,3, Yoshiyuki Ishii 1, Shigeru Kyuwa 1, Yoichiro Kuroda 2,3, Yasuhiro Yoshikawa 1,3
PMCID: PMC11529957  PMID: 15672684

Abstract

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.

1 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.

Keywords: mGluRs, PKA, synaptic transmission, Ca2+ imaging, synchronized Ca2+ spikes

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