Circuit Dynamics and Computational Neuroscience I.2.a Single-cell modeling Monday AM + Wednesday AM

2479 - A computational study of morphological effects on intracellular calcium dynamics in astrocytes

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I.2.a Single-cell modeling
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Abstract Body

Astrocytes, a subtype of glial cells in the brain, are actively involved in neuronal information processing and memory formation. Furthermore, they are linked to several neurodegenerative disorders and brain diseases. In Alzheimer’s disease, the whole cell body is swollen and processes are extended due to hypertrophy. An astrocyte participates in the neuronal activity by receiving neurotransmitters, i.e. glutamate, from an adjacent presynapse. This leads to the propagation of intra- and intercellular calcium waves. However, it is not clear what effect the astrocyte’s morphology has on these calcium dynamics. In this study, we present a finite element method-based model of single astrocytes with realistic 2D geometries resembling the healthy and the diseased state. The computational model simulates the propagation of intracellular calcium waves subsequent to stimulation by local glutamate. Following Oschmann et al. (2017), we include two spatially separated pathways of calcium release triggered by metabotropic glutamate receptors in the soma and glutamate transporters in the processes. Additionally, we have implemented calcium buffering. By simulating realistic astrocyte geometries with the same glutamate stimulus, we found out that the width of the astrocyte processes affects the spatial extent of the calcium propagation. The wider the process, the weaker the calcium wave as it diffuses to larger cytosol volume. To conclude, the morphology has a clear effect on the overall intracellular calcium dynamics, which both may be altered in neurodegenerative diseases.