Computational modeling of the relationship between morphological heterogeneity and functional responses in mouse hippocampal astrocytes.

IF 4.2 3区 医学 Q2 NEUROSCIENCES
Frontiers in Cellular Neuroscience Pub Date : 2024-10-17 eCollection Date: 2024-01-01 DOI:10.3389/fncel.2024.1474948
Anna Freund, Alexander Mayr, Peter Winkler, Rene Weber, Aapo Tervonen, Ron Refaeli, Kerstin Lenk
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引用次数: 0

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.

小鼠海马星形胶质细胞形态异质性与功能反应关系的计算建模
最近的研究表明,星形胶质细胞在形态和生理功能上具有异质性。星形胶质细胞整合突触信号,并释放钙离子,对活跃的神经元做出反应。由于这些钙信号高度依赖于细胞的形态,而细胞的形态在不同脑区和不同脑区之间都可能存在差异,因此这些钙信号尚未被完全理解。我们根据几何特征发现了小鼠海马 CA1 星形胶质细胞的结构异质性,将 741 个细胞分为六类。在这些细胞中,我们选择了 84 个细胞,根据共聚焦显微镜图像重建了它们的形态,并将其转换为高精细度的多室模型。我们应用计算生物物理模型模拟了这些三维细胞几何结构中的细胞内离子和 IP3 信号传递和扩散。细胞受到三种不同的谷氨酸刺激。钙主要在受刺激区和邻近区振荡,而在体细胞内则没有振荡。在比较受刺激区和邻近区的信号时,发现钙信号的峰值宽度、平均突出度和平均峰值振幅存在显著差异。总之,本研究强调了星形胶质细胞的复杂形态对细胞内离子信号转导的影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.90
自引率
3.80%
发文量
627
审稿时长
6-12 weeks
期刊介绍: Frontiers in Cellular Neuroscience is a leading journal in its field, publishing rigorously peer-reviewed research that advances our understanding of the cellular mechanisms underlying cell function in the nervous system across all species. Specialty Chief Editors Egidio D‘Angelo at the University of Pavia and Christian Hansel at the University of Chicago are supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
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