Temporal pattern and synergy influence activity of ERK signaling pathways during L-LTP induction

Abstract
Data availability
Article and author information
Metrics

Abstract

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 inter-trial 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 sensitivity facilitate ERK activation to diversity of temporal patterns.

Data availability

All model files are freely available on https://github.com/neurord/ERK/releases/tag/1.0.0All programs to analyze simulation output are available on https://github.com/neurord/NeuroRDanal/releases/tag/2.0.0.Programs for the statistical analysis and random forest analysis are available on https://github.com/neurord/ERK/tree/master/Analysis.These URLs are provided in the manuscript methods section. Model files are available from modelDB, accession number 267073.

Article and author information

Author details

Nadiatou T Miningou Zobon

George Mason University, Fairfax, United States

Competing interests
The authors declare that no competing interests exist.
Joanna Jędrzejewska-Szmek

Nencki Institute of Experimental Biology of Polish Academy of Sciences, Warsaw, Poland

Competing interests
The authors declare that no competing interests exist.
Kim T Blackwell

George Mason University, Fairfax, United States

For correspondence
kblackw1@gmu.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-4711-2344

Funding

National Institutes of Health (R01MH 117964)

Kim T Blackwell

National Science Foundation (1515686)

Kim T Blackwell

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.