TY - JOUR TI - Temporal pattern and synergy influence activity of ERK signaling pathways during L-LTP induction AU - Miningou Zobon, Nadiatou T AU - Jędrzejewska-Szmek, Joanna AU - Blackwell, Kim T A2 - Bhalla, Upinder Singh A2 - Calabrese, Ronald L VL - 10 PY - 2021 DA - 2021/08/10 SP - e64644 C1 - eLife 2021;10:e64644 DO - 10.7554/eLife.64644 UR - https://doi.org/10.7554/eLife.64644 AB - Long-lasting long-term potentiation (L-LTP) is a cellular mechanism of learning and memory storage. Studies have demonstrated a requirement for extracellular signal-regulated kinase (ERK) activation in L-LTP produced by a diversity of temporal stimulation patterns. Multiple signaling pathways converge to activate ERK, with different pathways being required for different stimulation patterns. To answer whether and how different temporal patterns select different signaling pathways for ERK activation, we developed a computational model of five signaling pathways (including two novel pathways) leading to ERK activation during L-LTP induction. We show that calcium and cAMP work synergistically to activate ERK and that stimuli given with large intertrial intervals activate more ERK than shorter intervals. Furthermore, these pathways contribute to different dynamics of ERK activation. These results suggest that signaling pathways with different temporal sensitivities facilitate ERK activation to diversity of temporal patterns. KW - ERK KW - SynGap KW - LTP KW - signaling pathway KW - hippocampus KW - epac JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -