Looking to the stars for answers: Strategies for determining how astrocytes influence neuronal activity.

Looking to the stars for answers: Strategies for determining how astrocytes influence neuronal activity.
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DOI:
10.1016/j.csbj.2022.07.052
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发表时间:
2022
影响因子:
6
通讯作者:
--
中科院分区:
生物学2区
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--
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星形胶质细胞是位于突触附近的神经回路的关键组成部分,使它们能够快速感知和响应神经元活动。一种反复观察到的星形胶质细胞活化的生物标志物是细胞内Ca2+水平的增加。这些星形胶质细胞Ca 2+信号经常被观察到从突触周星形胶质细胞突起到主要星形胶质细胞分支以及到索马或细胞体的各个细胞隔室中扩散。在这里,我们回顾最近的证据表明,星形胶质细胞的钙离子事件是显着异质性的形式和功能,通过星形胶质细胞合胞体传播,并直接联系到星形胶质细胞的能力,影响当地的神经元活动。由于星形胶质细胞的许多细胞功能可以与细胞内Ca2+信号传导联系在一起,并且这些事件的多样性和异质性变得更加明显,因此越来越需要设计新的实验策略来更好地理解这些信号如何与神经元活动并行演变。在这里,我们回顾了最近的进展,使表征亚细胞和群体范围内的星形胶质细胞钙离子动态。此外,我们还概述了在神经元或星形胶质细胞操作的背景下,同时在体内钙离子成像所需的实验设计,突出新的实验策略,使病毒载体,成像和定量技术的最新进展成为可能。通过结合使用这些试剂和方法,我们提供了一个概念框架,研究星形胶质细胞如何在功能上整合到神经回路中,以及它们在多大程度上影响和指导行为反应背后的突触活动。
Astrocytes are critical components of neural circuits positioned in close proximity to the synapse, allowing them to rapidly sense and respond to neuronal activity. One repeatedly observed biomarker of astroglial activation is an increase in intracellular Ca2+ levels. These astroglial Ca2+ signals are often observed spreading throughout various cellular compartments from perisynaptic astroglial processes, to major astrocytic branches and on to the soma or cell body. Here we review recent evidence demonstrating that astrocytic Ca2+ events are remarkably heterogeneous in both form and function, propagate through the astroglial syncytia, and are directly linked to the ability of astroglia to influence local neuronal activity. As many of the cellular functions of astroglia can be linked to intracellular Ca2+ signaling, and the diversity and heterogeneity of these events becomes more apparent, there is an increasing need for novel experimental strategies designed to better understand the how these signals evolve in parallel with neuronal activity. Here we review the recent advances that enable the characterization of both subcellular and population-wide astrocytic Ca2+ dynamics. Additionally, we also outline the experimental design required for simultaneous in vivo Ca2+ imaging in the context of neuronal or astroglial manipulation, highlighting new experimental strategies made possible by recent advances in viral vector, imaging, and quantification technologies. Through combined usage of these reagents and methodologies, we provide a conceptual framework to study how astrocytes functionally integrate into neural circuits and to what extent they influence and direct the synaptic activity underlying behavioral responses.
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