Abstract

Transduction and transmission of an input signal by a neuronal dendrite involves generation, integration and propagation of at least four kinds of information: Chemical concentration such as calcium ions, chemical modification such as phosphorylation cascades, conformational information such as allosteric modulations, and electrical signals such as membrane depolarisation. One cannot claim to understand neuronal function when focussing on a single aspect. However, developing models of the four requires using different formalisms. Furthermore running simulations implies widely different requirements in terms of compute power, storage or results and duration. I will present a few results we obtained about the synaptic function and plasticity in the striatal medium-spiny neuron, using models of signalling networks, allosteric regulations, single particle diffusion and multi-compartment electrical models. I will then discuss how we can sometimes encapsulate the results obtained at a certain level of resolution in order to increase the realism of more abstract models. I will end by outlining how one could envision to build a model striatal neuron that embodies chemical, biochemical and electrical signalling.

CV

Besides his experimental activity on the molecular basis of nicotine
addiction, Nicolas Le Novère has pursued research in computational biology for more than a decade. In 2003, he received the Jean-Marie Le Goff award, of the French Academy of Sciences, for his complete bioinformatic analysis of nicotinic acetylcholine receptors. Involved in Systems Biology since 1999, his main scientific interest is the study of signal transduction. He participated in several projects on bacterial chemotaxis, and is now focussing on modelling neuronal signalling. His team, at the EMBL-EBI, develop models of signal integration in the dendritic spines of striatal neurons, using continuous or discrete representations, at the population and mesoscopic levels. As one of the developers of the simulator StochSim, he participated in the creation of the Systems Biology Markup Language (SBML). He is now one of the official editors of SBML and a co-PI on the NIH-funded SBML development. He also plays a leading role in several other
standardisation efforts within Systems Biology, such as the Systems Biology Graphical Notation (SBGN), and the community standard on model quality (MIRIAM). In 2005 he launched BioModels Database, the reference resource for storing and distributing published quantitative models of biological processes.