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Modeling signal transduction in synaptic plasticity: comparison of models and methods

Long-term activity-dependent strengthening (LTP) and weakening (LTD) of synapses are two forms of synaptic plasticity. Both LTP and LTD participate in storing information and inducing processes that ultimately lead to learning and memory (e.g., [1]). Several mechanisms have been shown to be the reason for changes in synaptic strength, for example changes in neurotransmitter release, conductivity of receptors, numbers of receptors, numbers of active synapses, and structure of synapses [2]. At present, there are more than hundred molecules found important in LTP and LTD.

Several computational models, simple and more complex ones, have been developed to describe the mechanisms behind synaptic plasticity at the biochemical level. Simplest models have only one reversible reaction and most complicated ones have several hundred reactions.

In this study, we evaluate different computational models for describing LTP and LTD phenomena. Selected models, including both simplified (e.g., [3, 4]) and biophysically more detailed (e.g., [5, 6]) ones, are implemented, and their behavior is simulated with well-established deterministic and stochastic approaches [7]. Especially, we concentrate on the input-output relationship in simulations of the models. When using the same input, many of the models are found to give different responses. One of the reasons is that some of the models studied can mimic both the induction and maintenance of synaptic plasticity, whereas others are found to explain only the induction. Furthermore, the role of some specific molecules important in LTP and LTD is studied. Even thought the simplest models do not take into account all the details in biological knowledge, they can be used to predict different events, which is very important when modeling synaptic plasticity. The ultimate goal of this work is to provide realistic, yet simple enough models for describing LTP and LTD phenomena and addressing the general principles of information storage in neurons.


  1. Citri A, Malenka RC: Synaptic plasticity: multiple forms, functions, and mechanisms. Neuropsychopharmacology. 2008, 33 (1): 18-41. 10.1038/sj.npp.1301559.

    Article  PubMed  Google Scholar 

  2. Hayer A, Bhalla US: Molecular switches at the synapse emerge from receptor and kinase traffic. PLoS Comput Biol. 2005, 1 (2): 137-154. 10.1371/journal.pcbi.0010020.

    Article  CAS  PubMed  Google Scholar 

  3. Delord B, Berry H, Guigon E, Genet S: A new principle for information storage in an enzymatic pathway model. PLoS Comput Biol. 2007, 3 (6): e124-10.1371/journal.pcbi.0030124.

    Article  PubMed Central  PubMed  Google Scholar 

  4. Pi HJ, Lisman JE: Coupled phosphatase and kinase switches produce the tristability required for long-term potentiation and long-term depression. J Neurosci. 2008, 28 (49): 13132-13138. 10.1523/JNEUROSCI.2348-08.2008.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Lindskog M, Kim M, Wikström MA, Blackwell KT, Hellgren Kotaleski J: Transient calcium and dopamine increase PKA activity and DARPP-32 phosphorylation. PLoS Comput Biol. 2006, 2 (9): e119-10.1371/journal.pcbi.0020119.

    Article  PubMed Central  PubMed  Google Scholar 

  6. Graupner M, Brunel N: STDP in a bistable synapse model based on CaMKII and associated signaling pathways. PLoS Comput Biol. 2007, 3 (11): e221-10.1371/journal.pcbi.0030221.

    Article  PubMed Central  PubMed  Google Scholar 

  7. Manninen T, Linne ML, Ruohonen K: Developing Itô stochastic differential equation models for neuronal signal transduction pathways. Comput Biol Chem. 2006, 30 (4): 280-291. 10.1016/j.compbiolchem.2006.04.002.

    Article  CAS  PubMed  Google Scholar 

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This study was supported by the Academy of Finland, application numbers 129657 (Finnish Programme for Centres of Excellence in Research 2006-2011), 126556, and 137349, as well as the Finnish Foundation for Economic and Technology Sciences - KAUTE, Emil Aaltonen Foundation, Tampere University of Technology Graduate School, and Tampere Graduate School in Information Science and Engineering.

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Correspondence to Tiina Manninen.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Manninen, T., Hituri, K., Toivari, E. et al. Modeling signal transduction in synaptic plasticity: comparison of models and methods. BMC Neurosci 11 (Suppl 1), P190 (2010).

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  • Animal Model
  • Signal Transduction
  • Simple Model
  • Computational Model
  • General Principle