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Significance The expression of genes involved in hippocampal synaptic plasticity, learning, and memory requires that Ca2+ signals generated in spines, dendrites, or the soma by neuronal stimulation reach the nucleus. Here, we report that stimulation of hippocampal neurons induces Ca2+ release mediated by RyR2 channels, which contributes to nuclear Ca2+ signal generation. Suppression of RyR-mediated Ca2+ release inhibited the activity-induced phosphorylation of the nuclear transcriptional regulator CREB and the expression of the Npas4 transcription factor and RyR2, which play crucial roles in hippocampal memory processes. We propose that RyR-mediated Ca2+ release induced by neuronal stimulation, by promoting the sequential generation of nuclear Ca2+ signals, CREB phosphorylation, and Npas4/RyR2 up-regulation, plays a significant role in hippocampal synaptic plasticity and spatial memory processes.

proceedings of the national academy of sciences of the united states of america

RyR-mediated Ca<sup>2+</sup>release elicited by neuronal activity induces nuclear Ca<sup>2+</sup>signals, CREB phosphorylation, and Npas4/RyR2 expression

RyR-mediated Ca2+release elicited by neuronal activity induces nuclear Ca2+signals, CREB phosphorylation, and Npas4/RyR2 expression

RyR-mediated Ca²⁺release elicited by neuronal activity induces nuclear Ca²⁺signals, CREB phosphorylation, and Npas4/RyR2 expression