Modeling Signal Transduction Leading to Synaptic Plasticity: Evaluation and Comparison of Five Models

Abstract

An essential phenomenon of the functional brain is synaptic plasticity which is associated with changes in the strength of synapses between neurons. These changes are affected by both extracellular and intracellular mechanisms. For example, intracellular phosphorylation-dephosphorylation cycles have been shown to possess a special role in synaptic plasticity. We, here, provide the first computational comparison of models for synaptic plasticity by evaluating five models describing postsynaptic signal transduction networks. Our simulation results show that some of the models change their behavior completely due to varying total concentrations of protein kinase and phosphatase. Furthermore, the responses of the models vary when models are compared to each other. Based on our study, we conclude that there is a need for a general setup to objectively compare the models and an urgent demand for the minimum criteria that a computational model for synaptic plasticity needs to meet.

Challenges in Reproducibility, Replicability, and Comparability of Computational Models and Tools for Neuronal and Glial Networks, Cells, and Subcellular Structures

“…We implemented the chosen models with MATLAB Ⓡ . See more details in section 3 and in our previous publications (Manninen and Linne, 2008 ; Manninen et al, 2011 ) .…”

“…We were not able to completely implement the model by Zachariou et al ( 2013 ) because not all the information of the model was given in the original publication. More information about the reproducibility issues of the models can be found in our previous publications (Manninen and Linne, 2008 ; Manninen et al, 2011 ).…”

“…We were the first ones to provide a computational comparison of postsynaptic signal transduction models for synaptic plasticity (Manninen et al, 2011 ). We evaluated altogether five models, of which two were developed for hippocampal CA1 neurons (d'Alcantara et al, 2003 ; Kim et al, 2010 ), two were developed for striatal medium spiny neurons (Lindskog et al, 2006 ; Nakano et al, 2010 ), and one was a generic model (Hayer and Bhalla, 2005 ) (see Tables 2 , 5 ).…”

“…The model codes were neither intuitive nor commented. However, the database and simulation tool provided helpful explanation files to ease the use of the model files (see more details in Manninen et al, 2011 ). The model by Hayer and Bhalla ( 2005 ) we took from the Database of Quantitative Cellular Signaling (DOQCS, Sivakumaran et al, 2003 ) in MATLAB Ⓡ format.…”

“…The models by d'Alcantara et al ( 2003 ), Delord et al ( 2007 ), and Zachariou et al ( 2013 ) we used in the reproducibility studies. In the comparability studies (Manninen and Linne, 2008 ; Manninen et al, 2011 ), we tested the models by d'Alcantara et al ( 2003 ), Hayer and Bhalla ( 2005 ), Lindskog et al ( 2006 ), Delord et al ( 2007 ), Nakano et al ( 2010 ), and Kim et al ( 2010 ).…”