4.4 Review

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

Journal

NATURE REVIEWS NEUROSCIENCE
Volume 22, Issue 4, Pages 237-255

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41583-021-00441-z

Keywords

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Funding

  1. Ministere de l'Enseignement Superieur et de la Recherche
  2. Centre National de la Recherche Scientifique
  3. European Research Council [787340 Dyn-Syn-Mem]
  4. LabEx BRAIN [ANR-10-LABX-43, ANR-10-IDEX-03-02, ANR-16-CE13-0018, ANR-16-CE16-0026-01]
  5. Conseil Regional de Nouvelle Aquitaine
  6. Agence Nationale de la Recherche (ANR) [ANR-16-CE16-0026, ANR-16-CE13-0018] Funding Source: Agence Nationale de la Recherche (ANR)

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The brain is a highly complex organ, and advancements in imaging methods and molecular tools have revolutionized our understanding of its structure and function. By combining the latest molecular tools with imaging techniques, researchers are able to investigate neural function at a greater resolution than previously possible.
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.

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