Advanced imaging and labelling methods to decipher brain cell organization and function

• Published in: Nature reviews. Neuroscience 2021-04, Vol.22 (4), p.237-255
• Main Authors: Choquet, Daniel, Sainlos, Matthieu, Sibarita, Jean-Baptiste
• Format: Article
• Language: English
• Subjects: 631/378/340; 631/378/87; Animal Genetics and Genomics; Animals; Behavioral Sciences; Biological Techniques; Biomedical and Life Sciences; Biomedicine; Biosensors; Brain - cytology; Brain architecture; Brain mapping; Cytology; Humans; Labeling; Localization; Methods; Microscopy; Microscopy - methods; Neural circuitry; Neural networks; Neurobiology; Neuroglia - cytology; Neuroimaging; Neurons - cytology; Neurosciences; Observations; Review Article; Reviews; Staining and Labeling - methods
• ISSN: 1471-003X; 1471-0048; 1469-3178
• DOI: 10.1038/s41583-021-00441-z

The brain is arguably the most complex organ. The branched and extended morphology of nerve cells, their subcellular complexity, the multiplicity of brain cell types as well as their intricate connectivity and the scattering properties of brain tissue present formidable challenges to the understanding of brain function. Neuroscientists have often been at the forefront of technological and methodological developments to overcome these hurdles to visualize, quantify and modify cell and network properties. Over the last few decades, the development of advanced imaging methods has revolutionized our approach to explore the brain. Super-resolution microscopy and tissue imaging approaches have recently exploded. These instrumentation-based innovations have occurred in parallel with the development of new molecular approaches to label protein targets, to evolve new biosensors and to target them to appropriate cell types or subcellular compartments. We review the latest developments for labelling and functionalizing proteins with small localization and functionalized reporters. We present how these molecular tools are combined with the development of a wide variety of imaging methods that break either the diffraction barrier or the tissue penetration depth limits. We put these developments in perspective to emphasize how they will enable step changes in our understanding of the brain. The development of advanced imaging methods such as super-resolution microscopy and tissue imaging has revolutionized our approach to explore the brain. In this Review, Choquet and colleagues review how the latest molecular tools are combined with imaging techniques to investigate neural function at a greater resolution than previously possible.