The phosphorylation of CREB is an important step in the regulation of many activity-induced genes. Here the correlation between the increase in intrasomatic calcium concentration [Ca2+]i by metabotropic glutamate receptor (mGluR) activation and the phosphorylation of CREB was characterized in CA1 neurons of hippocampal slices. A short pulse-like application (≤500ms) of mGluR agonist (DHPG) leading to an [Ca2+]i increase up to 300nM proved to be sufficient to phosphorylate CREB. The mGluR-mediated CREB phosphorylation was dependent on the release of calcium from internal stores and the activation of the Ras/MAPK signal cascade. In addition, CREB was constitutively phosphorylated in postnatal hippocampal slices, which was dependent on the presence of ENOs (early network oscillations), a form of spontaneous intrinsic activity observed in the developing brain. Thus, ENOs may play an important role in driving developmental gene regulation.
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