Liu Langzhou, Gao Huayi, Li Jinyu, Chen Shangbin
Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology, Wuhan, China.
MoE Key Laboratory for Biomedical Photonics, School of Engineering Sciences, Huazhong University of Science and Technology, Wuhan, China.
Front Netw Physiol. 2023 Feb 10;3:1111306. doi: 10.3389/fnetp.2023.1111306. eCollection 2023.
Astrocytic fine processes are the most minor structures of astrocytes but host much of the Ca activity. These localized Ca signals spatially restricted to microdomains are crucial for information processing and synaptic transmission. However, the mechanistic link between astrocytic nanoscale processes and microdomain Ca activity remains hazily understood because of the technical difficulties in accessing this structurally unresolved region. In this study, we used computational models to disentangle the intricate relations of morphology and local Ca dynamics involved in astrocytic fine processes. We aimed to answer: 1) how nano-morphology affects local Ca activity and synaptic transmission, 2) and how fine processes affect Ca activity of large process they connect. To address these issues, we undertook the following two computational modeling: 1) we integrated the astrocyte morphological data from a recent study performed with super-resolution microscopy that discriminates sub-compartments of various shapes, referred to as nodes and shafts to a classic IPR-mediated Ca signaling framework describing the intracellular Ca dynamics, 2) we proposed a node-based tripartite synapse model linking with astrocytic morphology to predict the effect of structural deficits of astrocytes on synaptic transmission. Extensive simulations provided us with several biological insights: 1) the width of nodes and shafts could strongly influence the spatiotemporal variability of Ca signals properties but what indeed determined the Ca activity was the width ratio between nodes and shafts, 2) the connectivity of nodes to larger processes markedly shaped the Ca signal of the parent process rather than nodes morphology itself, 3) the morphological changes of astrocytic part might potentially induce the abnormality of synaptic transmission by affecting the level of glutamate at tripartite synapses. Taken together, this comprehensive model which integrated theoretical computation and morphological data highlights the role of the nanomorphology of astrocytes in signal transmission and its possible mechanisms related to pathological conditions.
星形胶质细胞的精细突起是星形胶质细胞中最小的结构，但却承载着大量的钙活性。这些局限于微区的局部钙信号对于信息处理和突触传递至关重要。然而，由于在研究这个结构尚未明确的区域时存在技术困难，星形胶质细胞纳米级突起与微区钙活性之间的机制联系仍不清楚。在本研究中，我们使用计算模型来理清星形胶质细胞精细突起中形态与局部钙动力学之间的复杂关系。我们旨在回答：1）纳米形态如何影响局部钙活性和突触传递，2）精细突起如何影响它们所连接的大突起的钙活性。为了解决这些问题，我们进行了以下两个计算建模：1）我们将最近一项使用超分辨率显微镜进行的研究中获得的星形胶质细胞形态学数据整合到一个经典的由肌醇 1,4,5 - 三磷酸（IP3）介导的钙信号框架中，该框架描述细胞内钙动力学，该研究区分了各种形状的亚区室（称为节点和轴），2）我们提出了一个基于节点的三方突触模型，将其与星形胶质细胞形态联系起来以预测星形胶质细胞结构缺陷对突触传递的影响。广泛的模拟为我们提供了几个生物学见解：1）节点和轴的宽度会强烈影响钙信号特性的时空变异性，但真正决定钙活性的是节点与轴的宽度比，2）节点与较大突起的连接显著塑造了母突起的钙信号，而不是节点形态本身，3）星形胶质细胞部分的形态变化可能通过影响三方突触处谷氨酸水平而潜在地诱导突触传递异常。综上所述，这个整合了理论计算和形态学数据的综合模型突出了星形胶质细胞纳米形态在信号传递中的作用及其与病理状况相关的可能机制
