title: Integration of biochemical and electrical signaling-multiscale model of the medium spiny neuron of the striatum.
abstract: Neuron behavior results from the interplay between networks of biochemical processes and electrical signaling. Synaptic plasticity is one of the neuronal properties emerging from such an interaction. One of the current approaches to study plasticity is to model either its electrical aspects or its biochemical components. Among the chief reasons are the different time scales involved, electrical events happening in milliseconds while biochemical cascades respond in minutes or hours. In order to create multiscale models taking in consideration both aspects simultaneously, one needs to synchronize the two models, and exchange relevant variable values. We present a new event-driven algorithm to synchronize different neuronal models, which decreases computational time and avoids superfluous synchronizations. The algorithm is implemented in the TimeScales framework. We demonstrate its use by simulating a new multiscale model of the Medium Spiny Neuron of the Neostriatum. The model comprises over a thousand dendritic spines, where the electrical model interacts with the respective instances of a biochemical model. Our results show that a multiscale model is able to exhibit changes of synaptic plasticity as a result of the interaction between electrical and biochemical signaling. Our synchronization strategy is general enough to be used in simulations of other models with similar synchronization issues, such as networks of neurons. Moreover, the integration between the electrical and the biochemical models opens up the possibility to investigate multiscale process, like synaptic plasticity, in a more global manner, while taking into account a more realistic description of the underlying mechanisms.
authors.affiliation: European Molecular Biology Laboratory, The European Bioinformatics Institute, Hinxton, Cambridge, United Kingdom.
authors.forename: Michele
authors.initials: M
authors.lastname: Mattioni
authors.forename: Nicolas
authors.initials: N
authors.lastname: Le Novère
mesh_terms: D000200:Action Potentials; D000465:Algorithms; D003198:Computer Simulation; D003342:Corpus Striatum / Q000502:physiology*; D049229:Dendritic Spines / Q000502:physiology; D004558:Electric Stimulation; D008959:Models, Neurological; D009473:Neuronal Plasticity; D009474:Neurons / Q000502:physiology*; D010766:Phosphorylation; D017470:Receptors, Glutamate / Q000378:metabolism; D015398:Signal Transduction; D013569:Synapses
chemical_list: D017470:Receptors, Glutamate; C492973:alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid subtype glutamate receptor, human