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FRINATEK-Fri prosj.st. mat.,naturv.,tek

Exciting times: Extreme modelling of excitable tissue (EMIx)

Alternative title: Modellering av eksiterbart vev på ekstrem skala (EMIx)

Awarded: NOK 12.0 mill.

Complex interactions between billions of nerve cells control our thoughts, emotions, behavior and movement. Nerve cells communicate via electrical signals generated by molecules and ions moving in, across and between the cells. Glial cells form networks stretching around the nerve cells and towards cerebral blood vessels, and contribute to the well being of the central nervous system. EMIx will develop mathematical and numerical models providing new insight into the intricate interplay between nerve cells and glial cells. We will develop models where the complicated geometry of each individual cell is represented explicitly - and that describe the coupling of electrical, chemical and mechanical processes at the cellular level. This level of detail requires both complex geometries and sophisticated mathematical models, and results in large systems of equations that call for efficient solvers and powerful computers. Resultantly, EMIx will introduce a new and extremely detailed computational framework for simulating brain tissue. The EMIx frameworks can potentially give sorely needed insight into both brain signalling, cerebral volume control and the role of glial cells in brain water clearance. Ultimately, EMIx will provide a new avenue of investigation for understanding physiological processes in the brain underlying oedema and neurodegenerative diseases.

Our brains are composed of excitable intertangled tissue consisting of neurons, glial cells, interstitial space and blood vessels, featuring an intricate and unique interplay between ion and water movement, electrical activity, and cellular swelling. Mathematical modelling and simulation could unravel elusive mechanisms underlying these processes, but key theory and technology are lacking. In response, the EMIx ambition is to establish mathematical and technological foundations for detailed modelling and simulation of electrical, chemical and mechanical interplay between brain cells, allowing for pioneering in-silico studies of brain signalling, volume balance and clearance. We will pursue an interdisciplinary approach targeting research questions in applied mathematics, scientific computing, and glio- and neuroscience via mathematical and computational techniques leveraging experimental findings. If successful, EMIx will introduce new mathematical frameworks for modelling electrical, chemical and mechanical interactions in detailed representations of excitable tissue via coupled mixed-dimensional partial differential equations. We will design and openly distribute numerical methods that allow for extreme high-resolution--high-realism simulations of such models. We will create innovative in-silico platforms for studying neuronal-glial-extracellular interactions at unprecedented detail, and create new insight into the mechanisms underlying the role of the brain's star cells (astrocytes) in brain ion and volume balance. Ultimately, EMIx will provide a new avenue of investigation for understanding physiological processes in the brain underlying oedema and neurodegenerative diseases.

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FRINATEK-Fri prosj.st. mat.,naturv.,tek