biostudies-literatureZhang YNINDS NIH HHSNLM NIH HHS294-7https://www.ebi.ac.uk/biostudies/studies/S-EPMC3267874biostudies-literatureUnknown15(2)Learning and memory are influenced by the temporal pattern of training stimuli. However, the mechanisms that determine the effectiveness of a particular training protocol are not well understood. We tested the hypothesis that the efficacy of a protocol is determined in part by interactions among biochemical cascades that underlie learning and memory. Previous findings suggest that the protein kinase A (PKA) and extracellular signal-regulated kinase (ERK) cascades are necessary to induce long-term synaptic facilitation (LTF) in Aplysia, a neuronal correlate of memory. We developed a computational model of the PKA and ERK cascades and used it to identify a training protocol that maximized PKA and ERK interactions. In vitro studies confirmed that the protocol enhanced LTF. Moreover, the protocol enhanced the levels of phosphorylation of the transcription factor CREB1. Behavioral training confirmed that long-term memory also was enhanced by the protocol. These results illustrate the feasibility of using computational models to design training protocols that improve memory.Nature neuroscienceComputational design of enhanced learning protocols.PMC3267874P01 NS038310-10R01 NS073974R01 NS019895P01 NS038310R01 NS019895-29T15LM007093R01 NS073974-02T15 LM007093-10T15 LM007093Liu RYCleary LJSmolen PHeberton GAZhang YByrne JHBaxter DAfalseComputational design of enhanced learning protocols.Learning and memory are influenced by the temporal pattern of training stimuli. However, the mechanisms that determine the effectiveness of a particular training protocol are not well understood. We tested the hypothesis that the efficacy of a protocol is determined in part by interactions among biochemical cascades that underlie learning and memory. Previous findings suggest that the protein kinase A (PKA) and extracellular signal-regulated kinase (ERK) cascades are necessary to induce long-term synaptic facilitation (LTF) in Aplysia, a neuronal correlate of memory. We developed a computational model of the PKA and ERK cascades and used it to identify a training protocol that maximized PKA and ERK interactions. In vitro studies confirmed that the protocol enhanced LTF. Moreover, the protocol enhanced the levels of phosphorylation of the transcription factor CREB1. Behavioral training confirmed that long-term memory also was enhanced by the protocol. These results illustrate the feasibility of using computational models to design training protocols that improve memory.2011-01-01T00:00:00Z2011 Dec2020-10-31T09:26:39Z2019-03-27T00:48:31ZS-EPMC32678742219782910.1038/nn.2990