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

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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).