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

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. 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.

Regulation of spontaneous Ca2+ spikes by metabotropic glutamate receptors in primary cultures of rat cortical neurons

“…We showed that LY341495 did not affect spontaneous Ca 2+ spikes by itself. Yasumoto et al (2004) showed that the inhibition of group II mGluRs by (2S)‐a‐ethylglutamic acid increased the frequency of spontaneous Ca 2+ spikes in primary cultures of mouse cortical neurons. The differences in the effects of group II mGluRs antagonists between our results and their report might be due to the level of the extracellular glutamate concentration in assay buffer.…”

“…Insofar as trans‐ACPD and (S)‐4CPG are nonselective mGluR ligands, the contributions of each mGluR subtype to spontaneous Ca 2+ spike formation remain to be clearly determined. Although Yasumoto et al, (2004) showed that a group II mGluR antagonist, (2S)‐a‐ethylglutamic acid, increased the frequency of spontaneous Ca 2+ spikes in primary cultures of mouse cortical neurons, no selective agonist of group II mGluRs has been tested for effects on spontaneous Ca 2+ spikes.…”