Computational design of enhanced learning protocols

• Published in: Nature neuroscience Vol. 15; no. 2; pp. 294 - 297
• Main Authors: Zhang, Yili, Liu, Rong-Yu, Heberton, George A, Smolen, Paul, Baxter, Douglas A, Cleary, Leonard J, Byrne, John H
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.02.2012; Nature Publishing Group
• Subjects: 631/378/116; 631/378/1595; 631/378/2591; 631/378/2649; Analysis; Analysis of Variance; Animal Genetics and Genomics; Animals; Aplysia; Behavioral Sciences; Biological Techniques; Biomedical and Life Sciences; Biomedicine; Cells, Cultured; Coculture Techniques; Computational neuroscience; Computer Simulation; CREB-Binding Protein - metabolism; Cyclic AMP-Dependent Protein Kinases - metabolism; Electric Stimulation; Extracellular Signal-Regulated MAP Kinases - metabolism; Functional Laterality; Ganglia, Invertebrate - cytology; Humans; Hypotheses; Kinases; Learning; Learning - drug effects; Learning - physiology; Long-Term Potentiation - physiology; Memory; Methods; Models, Biological; Motor Neurons - physiology; Neurobiology; Neurosciences; Phosphorylation; Physiological aspects; Protocol; Sensory Receptor Cells - physiology; Serotonin - pharmacology; Signal Transduction; Transcription factors
• ISSN: 1097-6256; 1546-1726
• DOI: 10.1038/nn.2990

The authors use computational modeling to design an optimized learning protocol that takes into account the precise timing of molecular signaling cascades that are necessary for synaptic facilitation. This study demonstrates how learning and memory can be enhanced by the coordination of biochemical mechanisms and training 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.