Computational design of enhanced learning protocols. Academic Article uri icon


  • 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.

published proceedings

  • Nat Neurosci

altmetric score

  • 37.298

author list (cited authors)

  • Zhang, Y., Liu, R., Heberton, G. A., Smolen, P., Baxter, D. A., Cleary, L. J., & Byrne, J. H.

citation count

  • 67

complete list of authors

  • Zhang, Yili||Liu, Rong-Yu||Heberton, George A||Smolen, Paul||Baxter, Douglas A||Cleary, Leonard J||Byrne, John H

publication date

  • December 2011