CRCNS: US-German Collaboration: Role of Astrocytes in Cortical Information Processing

皮质由两种主要的细胞类型组成：神经元和神经胶质。 大多数关于皮层功能的研究主要集中在神经元在信号处理中的作用。神经胶质细胞，包括星形胶质细胞，被认为是脑功能的次要参与者，为神经元提供物理和代谢支持。在初级视皮层（V1），精确的神经元反应和表征被认为是锚视觉处理。然而，星形胶质细胞接触突触以及血管，最近的证据表明，星形胶质细胞接受突触输入和影响神经元以及血管反应。过去十年积累的成果导致了？三重突触概念，其中皮质中的兴奋性突触由突触前、突触后和星形胶质细胞元件组成。 这一提议的一个过于复杂和新颖的主题是星形胶质细胞与神经元在突触传递和可塑性方面的伙伴关系。任何完整的框架，理解和建模的网络基础的皮质反应必须考虑星形胶质细胞和神经元的贡献。 本研究的目的是结合联合收割机的实验和计算机模拟方法来了解星形胶质细胞在视皮层神经元反应的产生、发展和可塑性中的作用。 星形胶质细胞生物学和生理学的许多方面已经在体外进行了描述，但对星形胶质细胞在完整功能回路中的作用知之甚少。该项目将利用新的实验方法，包括特定的细胞标记物，细胞功能的光学探针，以及具有光学报告的基因工程小鼠，这些方法提供了新的方法来研究神经元和星形胶质细胞在视觉皮层反应和表征中的合作作用。美国Mriganka Sur实验室率先使用这些方法，结合细胞的体内双光子钙成像，内在信号的光学成像和电生理记录，研究星形胶质细胞对视觉处理的影响。 该项目的建模部分将开发第一个视觉皮质网络模型，除了神经元兴奋和抑制之外，还包括星形胶质细胞对突触传递的影响。克劳斯·奥伯迈耶（Klaus Obermayer）的德国实验室对视觉皮层网络如何产生、发展和改变紧急反应的计算理解做出了开创性的贡献。Sur和Obermayer小组以前的共同努力在揭示视觉皮层网络的操作机制、地图结构对皮层网络功能的影响以及特征选择性反应的动态方面具有影响力。在每种情况下，计算模型影响实验，反之亦然。该项目由计算神经科学合作研究和国际科学与工程办公室联合资助。 德国教育和研究部（BMBF）正在资助一个配套项目。

The cortex consists of two major cell types: neurons and glia. Most research in cortical function has focused primarily on the role of neurons in signal processing. Glial cells, including astrocytes, have been considered as secondary actors in brain function, providing physical and metabolic support to neurons. In primary visual cortex (V1), precise neuronal responses and representations are considered to anchor visual processing. However, astrocytes contact synapses as well as blood vessels, and recent evidence suggests that astrocytes receive synaptic inputs and influence neuronal as well as vascular responses. The accumulated results of the past decade have led to the ?tripartite synapse? concept, in which excitatory synapses in cortex are composed of a presynaptic, a postsynaptic, and an astrocytic element. An over-arching and novel theme of this proposal is that astrocytes partner with neurons in synaptic transmission and plasticity. Any complete framework for understanding and modeling the network basis of cortical responses must account for both astrocytic and neuronal contributions. The goal of this proposal is to combine experimental and computational modeling approaches to understand the role astrocytes play in the generation, development and plasticity of neuronal responses in visual cortex. Many aspects of astrocyte biology and physiology have been described in vitro, but little is known about the role of astrocytes in the context of intact functional circuits. This project will utilize novel experimental approaches, including specific cellular markers, optical probes of cellular function, and genetically engineered mice with optical reporters, that provide new ways to examine the cooperative roles of neurons and astrocytes in visual cortex responses and representations. The US laboratory of Mriganka Sur has pioneered the use of these approaches, in combination with in vivo two-photon calcium imaging of cells, optical imaging of intrinsic signals, and electrophysiological recording, to study the influence of astrocytes on visual processing. The modeling portion of this project will develop the first network models of visual cortex to include astrocyte influences on synaptic transmission, in addition to neuronal excitation and inhibition. The German laboratory of Klaus Obermayer has made seminal contributions to a computational understanding of how visual cortex networks generate, develop and alter emergent responses. Previous joint efforts of the Sur and Obermayer groups have been influential in revealing operating regimes of visual cortex networks, the influence of map structure on cortical network function, and the dynamics of feature-selective responses. In each instance, computational models influenced experiments, and vice versa.This project is jointly funded by Collaborative Research in Computational Neuroscience and the Office of International Science and Engineering. A companion project is being funded by the German Ministry of Education and Research (BMBF).