RyR-mediated Ca <sup>2+</sup> release elicited by neuronal activity induces nuclear Ca <sup>2+</sup> signals, CREB phosphorylation, and Npas4/RyR2 expression
Pedro Lobos, Alex Córdova, Ignacio Vega-Vásquez, Omar A. Ramírez, Tatiana Adasme, Jorge Toledo, Mauricio Cerda, Steffen Härtel, Andrea Paula-Lima, Cecilia Hidalgo
Abstract
Significance The expression of genes involved in hippocampal synaptic plasticity, learning, and memory requires that Ca 2+ signals generated in spines, dendrites, or the soma by neuronal stimulation reach the nucleus. Here, we report that stimulation of hippocampal neurons induces Ca 2+ release mediated by RyR2 channels, which contributes to nuclear Ca 2+ signal generation. Suppression of RyR-mediated Ca 2+ 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 Ca 2+ release induced by neuronal stimulation, by promoting the sequential generation of nuclear Ca 2+ signals, CREB phosphorylation, and Npas4/RyR2 up-regulation, plays a significant role in hippocampal synaptic plasticity and spatial memory processes.