Modelling of calcium Dynamics in Astrocyte Geometries
Khalid, Muhammad Uzair
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Astrocytes have historically been referred to as support cells in the central nervous system. In the past two decades, astrocytes have witnessed more interest due to the realization that they are involved in cognitive functions of brain such as information processing, thinking and memory formation as well as in several neurodegenerative diseases. Astrocytes communicate bi-directionally with synapses via uptake and potentially release of gliotransmitters. This communication indirectly affects the neuronal activity by propagating waves of Ca2+ intracellularly and intercellularly. However, the effect of astrocyte geometry on the propagation of these Ca2+ waves is unclear. In this thesis, I present my findings from a geometry-based computational model to highlight how the geometry of an astrocyte affects the Ca2+ signalling. We investigate how the amplitude modulation encoding of Ca2+ oscillations propagate from the astrocytic process to the soma of the cell. We start with the model of De Pitta et al. (2009) and implement it computationally using finite element method (FEM) in COMSOL Multiphysics, thereby, adding astrocyte geometry to their model. Using theoretical astrocyte geometries, we also study the role of amplitude and frequency of glutamate stimulus and how does it affect the elevations in intracellular Ca2+ concentrations. Our implementation can be used to determine the amplitude and frequency of synaptically-evoked Ca2+ oscillations at any selected locations in an astrocyte geometry with respect to time. The findings from this research work were published in Khalid et al. 2017. Based on the results obtained in this thesis, I conclude that the shape of an astrocyte does have an impact on the intracellular Ca2+ dynamics. When a fixed glutamate stimulus is used in different geometries, Ca2+ waves tends to propagate with higher concentrations near narrow ends of the astrocytic processes in comparison to the wider astrocytic process. Additionally, I found that the amplitude, frequency and pulse width of the glutamate stimulus which binds to the astrocytic membrane receptors has a major role in determining the dynamic of Ca2+ wave propagation.