AUTHOR=Freund Anna , Mayr Alexander , Winkler Peter , Weber Rene , Tervonen Aapo , Refaeli Ron , Lenk Kerstin TITLE=Computational modeling of the relationship between morphological heterogeneity and functional responses in mouse hippocampal astrocytes JOURNAL=Frontiers in Cellular Neuroscience VOLUME=18 YEAR=2024 URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2024.1474948 DOI=10.3389/fncel.2024.1474948 ISSN=1662-5102 ABSTRACT=

Recent studies indicate that astrocytes show heterogeneity in morphology and physiological function. They integrate synaptic signals and release calcium in reaction to active neurons. These calcium signals are not yet fully understood as they are highly dependent on the cell's morphology, which can vary across and within brain regions. We found structural heterogeneity among mouse hippocampal CA1 astrocytes based on geometric features, clustering 741 cells into six classes. Of those, we selected 84 cells and reconstructed their morphology based on confocal microscope images and converted them into multi-compartment models with a high detailedness. We applied a computational biophysical model simulating the intracellular ion and IP3 signaling and diffusion in those 3D cell geometries. The cells were stimulated with three different glutamate stimuli. Calcium mainly oscillated in the stimulated and the neighboring compartment but not in the soma. Significant differences were found in the peak width, mean prominence, and mean peak amplitude of the calcium signal when comparing the signals in the stimulated and neighboring compartments. Overall, this study highlights the influence of the complex morphology of astrocytes on intracellular ionic signaling.