title: Integrated multiscale modeling of the nervous system: predicting changes in hippocampal network activity by a positive AMPA receptor modulator.
abstract: 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.
authors.affiliation: Department of Biomedical Engineering, University of Southern California, Los Angeles, CA 90089-1111, USA. jbouteil@usc.edu
authors.forename: Jean-Marie C
authors.initials: JM
authors.lastname: Bouteiller
authors.forename: Sushmita L
authors.initials: SL
authors.lastname: Allam
authors.forename: Eric Y
authors.initials: EY
authors.lastname: Hu
authors.forename: Renaud
authors.initials: R
authors.lastname: Greget
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ambert
authors.forename: Anne Florence
authors.initials: AF
authors.lastname: Keller
authors.forename: Serge
authors.initials: S
authors.lastname: Bischoff
authors.forename: Michel
authors.initials: M
authors.lastname: Baudry
authors.forename: Theodore W
authors.initials: TW
authors.lastname: Berger
mesh_terms: D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000502:physiology*; D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D008959:Models, Neurological; D009415:Nerve Net / Q000166:cytology / Q000502:physiology*; D018091:Receptors, AMPA / Q000378:metabolism*
chemical_list: D018091:Receptors, AMPA