Stochastic modeling of neuronal signaling
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1
Tampere University of Technology, Finland
The time evolution of biochemical systems in neurons is traditionally modeled using deterministic ordinary differential equations (ODEs). Chemical reactions, however, are random in nature, and the deterministic approach is valid only for a restricted class of systems. Stochastic models take random fluctuations into account and are thus more realistic. Biochemical reactions can be modeled stochastically using numerous different methods. An ideal model would have the following three important properties. First, the model should be as realistic as possible, second, the mathematical method should be easily implementable as a computer algorithm, and third, the algorithm should be computationally effective. Naturally, all these three conditions cannot be fulfilled at the same time.
Some realistic modeling approaches can be derived directly from chemical kinetics without making any approximations. Such approaches are called exact. A good example of an exact modeling approach is the stochastic simulation algorithm (SSA) developed by Gillespie. The SSA is applicable when the molecular populations in the system are small, but it becomes computationally inefficient when the numbers of molecules increase. In order to construct stochastic models that can be effectively simulated, new mathematical approaches have to be explored.
As an approximate method also stochastic differential equations (SDEs) have been considered a promising way to model biochemical reactions stochastically. The SDE approach is attractive especially if we consider a system for which the SSA is computationally inefficient and the traditional deterministic ODE approach cannot be used as a good approximation. SDE models treat the chemical populations as real numbers and the construction of the model is based on the law of mass action, similarly as the construction of the traditional deterministic modeling approach. The SDE model, however, takes the random fluctuations into account by describing the time evolution of the system with the stochastic Itô process instead of the deterministic set of ODEs. The Itô process is basically a set of coupled stochastic differential equations. Although SDE modeling usually leads to equations that cannot be solved analytically, the solutions can be approximated numerically using different numerical integration methods. Thus, SDEs provide a mathematically rigorous way to construct models that can be simulated effectively.
In order to investigate how well the SDE approach models biochemical systems, the results have to be compared with experimental data or with the simulation results from some exact simulation procedure. In this study, we use the methodology of spectral analysis to compare the simulation results of the SDE model and the SSA. As case studies, we consider e.g. calcium binding and protein kinase C (PKC) signal transduction pathway. We investigate the nature of noise in different modeling approaches and try to interpret the meaning of the noise in real biological systems. The main goal of our study is to find the most essential components and parameters in the SDE model and to adjust them so that the model is capable of giving similar results as the SSA. The simulations are carried out using the distributed computing resources (GRID) provided by Techila Technologies Ltd.
Conference:
Neuroinformatics 2008, Stockholm, Sweden, 7 Sep - 9 Sep, 2008.
Presentation Type:
Poster Presentation
Topic:
Computational Neuroscience
Citation:
Intosalmi
J,
Manninen
T,
Ruohonen
K and
Linne
M
(2008). Stochastic modeling of neuronal signaling.
Front. Neuroinform.
Conference Abstract:
Neuroinformatics 2008.
doi: 10.3389/conf.neuro.11.2008.01.023
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Received:
28 Jul 2008;
Published Online:
28 Jul 2008.
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Correspondence:
Jukka Intosalmi, Tampere University of Technology, Tampere, Finland, jukka.intosalmi@tut.fi