Neural-Glial Communication Networks: A Computational Approach

大脑功能的新图像是神经元和星形胶质细胞之间的复杂通信网络。现在已经清楚的是，星形胶质细胞-大脑中数量最多的非神经元细胞类型-是神经元的重要伙伴。星形胶质细胞倾听神经元的声音，对其做出反应，并与神经元进行交谈，从而调节它们的功能。因此，了解神经元和星形胶质细胞的复杂通信网络对于理解大脑具有重要意义。虽然这一新兴的研究领域到目前为止主要由细胞和分子生物学方法驱动，但该项目的主要目标是增加一套新的工具-数学和计算建模-可以为探索复杂的神经胶质细胞通信网络提供新的途径。一个数学/计算模型-由功能耦合单元组成-产生了一个独特的概念框架，可以对生物过程进行分类并生成预测。具体而言，该奖项将使人们能够探索星形胶质细胞中响应神经元活动的信号生成，信号通过星形胶质细胞网络的空间传播，以及传播信号对神经元回路的影响，神经元和星形胶质细胞之间相互作用的所有重要方面。这些相互作用的现实的数学模型将被开发。在了解神经胶质细胞通信系统的重要组成部分之后，可以对具有类似于皮质中的结构的神经元电路进行建模，并将探索星形胶质细胞对网络的影响。这些目标将通过在细胞生物学家的实验室中使用现代成像工具来实现，其中细胞内钙信号的关键数据将用于开发神经胶质细胞相互作用的逼真数学模型。该项目的意义远远超出了理解中枢神经系统中星形胶质细胞和神经元的通信网络的具体目的。定量和概念性的了解神经胶质细胞的相互作用，可以提供一个基础，更好地了解大脑疾病，如偏头痛和癫痫，其中胶质成分是强烈怀疑。此外，了解细胞内钙信号传导，星形胶质细胞之间的重要信号传导途径，对于各种组织中的信号传导至关重要，例如肝脏，其中它有助于酶的释放，以及角膜和支气管上皮，其中它涉及伤口反应。

The emerging picture of brain function is that of a complex communication network between neurons and astrocytes. It has now become clear that astrocytes - the most numerous types of non-neuronal cells in the brain - are important partners to the neurons. Astrocytes listen to the neuronal chatter, respond to it and talk back to the neurons, thus modulating their functions. Understanding the complex communication network of neurons and astrocytes is therefore significant for the understanding of the brain. While this emerging field of research has been driven so far predominantly by methods of cellular and molecular biology, the main objective of this project is to add a new set of tools - mathematical and computational modeling - that can offer new avenues to explore the complex neural-glial communication network. A mathematical/computational model - consisting of functional coupled units - generates a unique conceptual framework that allows categorizing biologic processes and generating predictions.Specifically, this award will enable an exploration of the generation of signals in astrocytes in response to neuronal activity, the spatial spread of the signal through the network of astrocytes, and the effect of the spreading signal back on the neuronal circuit, all significant aspects of interactions between neurons and astrocytes. Realistic mathematical models of these interactions will be developed. After the significant components of the neural-glial communication system are understood, neuronal circuitry with an architecture resembling that in the cortex can be modeled, and the influence of astrocytes on the network will be explored. These goals will be achieved through the use of modern imaging tools employed in a cell biologist's laboratory, from which critical data on intracellular calcium signaling will be used to develop realistic mathematical modeling of the neural-glial interactions.This project has significance far beyond the specific purpose of understanding the communication network of astrocytes and neurons in the central nervous system. Quantitative and conceptual understanding of neural-glial interactions may provide a basis for a better understanding of brain disorders such as migraine and epilepsy, in which a glial component is strongly suspected. Additionally, understanding of the intracellular calcium signaling, an important signaling pathway between astrocytes, is of critical importance for signaling in a variety of tissues, such as liver, where it contributes to the release of enzymes, and in corneal and bronchial epithelia where it is involved with wound response.