The extracellular matrix (ECM) occupies the space between both neurons and glial cells and thus provides a microenvironment that regulates multiple aspects of neural activities. Because of the vital role of ECM as a natural environment of cells in vivo, there is a growing interest to develop methodology allowing for the detailed structural and functional analyses of ECM. In this chapter, we provide the detailed overview of current microscopic methods used for ECM analysis and also describe general labeling strategies for ECM visualization. Since ECM remodeling involves the proteolytic cleavage of ECM, we will also describe current experimental approaches to image the proteolytic reorganization and/or degradation of ECM. The special focus of this chapter is set to the application of Förster resonance energy transfer-based approaches to monitor intracellular and extracellular matrix functions with high spatiotemporal resolution.

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