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Multiscale modeling and simulations to bridge molecular and cellular scales

Biophysical basis of astroglial physiology probed with realistic simulation tool ASTRO

speaker: Leonid Savtchenko (University College London)

abstract: Leonid P. Savtchenko1, Christian Henneberger1,2,3, Lucie Bard1, Thomas P. Jensen1, James P. Reynolds1, Igor Kraev4, Mikola Medvedev4, Michael G. Stewart4, Dmitri A. Rusakov1 1 UCL Institute of Neurology, University College London, UK; 2 Institute of Cellular Neuro- sciences, University of Bonn, Germany 3 German Center of Neurodegenerative Diseases (DZNE), Bonn, Germany 4 The Open University, Milton Keynes, UK

Electrically non-excitable astroglia take up neurotransmitters, bu er extracellular K+ and gen- erate intracellular Ca2+ waves that release molecular regulators of neural circuitry. The underlying cellular machinery remains enigmatic, mainly because the nanoscopic, sponge-like astrocyte morphol- ogy has been dicult to access experimentally and explore theoretically. Here, we have systematically evaluated the multi-scale morphology of protoplasmic astroglia and developed computational tools to construct a realistic multi-compartmental astrocyte model that can be biophysically interrogated in the NEURON computational environment. As a proof of concept, we simulated and explored a hippocampal astrocyte in silico against a battery of physiological and imaging tests. Exploring the model has unveiled some of the basic features of astroglial physiology inaccessible in experiments, such as membrane voltage propagation, dynamic K+ redistribution, or intracellular Ca2+ bu ering. The modelling approach has been implemented as a simulation tool ASTRO, with an interactive interface and the capacity to run resource-consuming computations on a remote cluster or cloud. ASTRO paves the way to the mechanistic interpretation of experimental observations in astroglia.


timetable:
Fri 5 Oct, 9:45 - 10:45, Aula Dini
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