Integrated Multiscale Modeling of the Nervous System: Predicting Changes in Hippocampal Network Activity by a Positive AMPA Receptor Modulator

Jean-Marie Bouteiller (1) , Sushmita Allam (2) , Hu Eric Y. (2) , Greget Renaud (3) , Ambert Nicolas (3) , Anne Florence Keller (3) , Serge Bischoff (3) , Michel Baudry (4) , Theodore W Berger (2)

1 Department of Biomedical Engineering
2 Department of Biomedical Engineering
3 Rhenovia Pharma
4 Department of Biomedical Engineering and Center for Neural Engineering

One of the fundamental characteristics of the brain is its hierarchical organization. Scales in both space and time that must be considered when integrating across hierarchies of the nervous system are sufficiently great as to have impeded the development of routine multilevel modeling methodologies. Complex molecular interactions at the level of receptors and channels regulate activity at the level of neurons; interactions between multiple populations of neurons ultimately give rise to complex neural systems function and behavior. This spatial complexity takes place in the context of a composite temporal integration of multiple, different events unfolding at the millisecond, second, minute, hour, and longer time scales. In this study, we present a multiscale modeling methodology that integrates synaptic models into single neuron, and multineuron, network models. We have applied this approach to the specific problem of how changes at the level of kinetic parameters of a receptor-channel model are translated into changes in the temporal firing pattern of a single neuron, and ultimately, changes in the spatiotemporal activity of a network of neurons. These results demonstrate how this powerful methodology can be applied to understand the effects of a given local process within multiple hierarchical levels of the nervous system.

Mots clés: Ampakine; bioinformatics; biological system modeling; EONS; glutamate receptor modulator; multi-scale; nervous system; neuronal firing; RHENOMS; synaptic integration; synapse model

Domaines: Modélisation et simulation

Jean-Marie Bouteiller, Sushmita Allam, Hu Eric Y., Greget Renaud, Ambert Nicolas, et al.. Integrated Multiscale Modeling of the Nervous System: Predicting Changes in Hippocampal Network Activity by a Positive AMPA Receptor Modulator. IEEE Transactions on Biomedical Engineering, 2011, 58 (10), pp.3008-3011. ⟨10.1109/TBME.2011.2158605⟩. ⟨hal-00851888⟩