Glutamate regulates the frequency of spontaneous synchronized Ca ²⁺ spikes through group II metabotropic glutamate receptor in cultured mouse cortical networks

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.