title: Modeling of the nervous system: from molecular dynamics and synaptic modulation to neuron spiking activity.
abstract: The brain is a perfect example of an integrated multi-scale system, as the complex interactions taking place at the molecular level regulate neuronal activity that further modifies the function of millions of neurons connected by trillions of synapses, ultimately giving rise to complex function and behavior at the system level. Likewise, the spatial complexity is accompanied by a complex temporal integration of events taking place at the microsecond scale leading to slower changes occurring at the second, minute and hour scales. In the present study we illustrate our approach to model and simulate the spatio-temporal complexity of the nervous system by developing a multi-scale model integrating synaptic models into the neuronal and ultimately network levels. We apply this approach to a concrete example and demonstrate how changes at the level of kinetic parameters of a receptor model are translated into significant changes in the firing of a pyramidal neuron. These results illustrate the abilities of our modeling approach and support its direct application to the evaluation of the effects of drugs, from functional target to integrated system.
authors.affiliation: Department of Biomedical Engineering, University of Southern California, 1042 Downey Way, DRB Building, 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 F
authors.initials: AF
authors.lastname: Keller
authors.forename: Fabien
authors.initials: F
authors.lastname: Pernot
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: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D003198:Computer Simulation; D006801:Humans; D008959:Models, Neurological; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology*; D010078:Oxazines / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D018091:Receptors, AMPA / Q000819:agonists* / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D010078:Oxazines; D018091:Receptors, AMPA; C414782:2H,3H,6aH-pyrrolidino(2'',1''-3',2')1,3-oxazino(6',5'-5,4)benzo(e)1, 4-dioxan-10-one