新生肌动蛋白动力学以及发育中的神经细胞网络中肌动蛋白停滞对钙动力学的破坏。

Nascent actin dynamics and the disruption of calcium dynamics by actin arrest in developing neural cell networks.

作者信息

Gates Sylvester J, Alvarez Phillip H, O'Neill Kate M, Cao Kan, Losert Wolfgang

机构信息

Institute for Physical Sciences and Technology, University of Maryland College Park, College Park, MD, USA.

Cellular Biology and Molecular Genetics, University of Maryland College Park, College Park, MD, USA.

出版信息

Commun Biol. 2025 Jul 1;8(1):978. doi: 10.1038/s42003-025-08342-y.

Abstract

Waves and oscillations are key to information flow and processing in the brain. Recent work shows that, in addition to electrical activity, biomechanical signaling can also be excitable and support self-sustaining oscillations and waves. Here, we measured the biomechanical dynamics of actin polymerization in neural precursor cells (NPC) during their differentiation into populations of neurons and astrocytes. Using fluorescence-based live-cell imaging, we analyzed the dynamics of actin and calcium signals. The size and localization of actin dynamics adjusts to match functional needs throughout differentiation, enabling the initiation and elongation of processes and, ultimately, the formation of synaptic and perisynaptic structures. Throughout differentiation, actin remains dynamic in the soma, with many cells showing notable rhythmic character. Arrest of actin dynamics increases the slower time scale (likely astrocytic) calcium dynamics by 1) decreasing the duration and increasing the frequency of calcium spikes and 2) decreasing the time-delay cross-correlations in the networks. These results are consistent with the transition from an overdamped system to a spontaneously oscillating system and suggest that dynamic actin may dampen calcium signals. We conclude that mechanochemical interventions can impact calcium signaling and, thus, information flow in the brain.

摘要

波和振荡是大脑中信息流和信息处理的关键。最近的研究表明,除了电活动外,生物力学信号也具有兴奋性,并能支持自持振荡和波。在这里,我们测量了神经前体细胞(NPC)在分化为神经元和星形胶质细胞群体过程中肌动蛋白聚合的生物力学动力学。利用基于荧光的活细胞成像技术,我们分析了肌动蛋白和钙信号的动力学。在整个分化过程中,肌动蛋白动力学的大小和定位会进行调整以匹配功能需求,从而实现突起的起始和伸长,并最终形成突触和突触周围结构。在整个分化过程中,肌动蛋白在胞体中保持动态,许多细胞表现出显著的节律性特征。肌动蛋白动力学的停滞会通过以下方式增加较慢时间尺度(可能是星形胶质细胞的)钙动力学:1)减少钙尖峰的持续时间并增加其频率;2)减少网络中的时间延迟互相关。这些结果与从过阻尼系统向自发振荡系统的转变一致,并表明动态肌动蛋白可能会抑制钙信号。我们得出结论,机械化学干预可以影响钙信号传导,进而影响大脑中的信息流。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f10b/12218117/4bac59c9ac27/42003_2025_8342_Fig1_HTML.jpg

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