Expansion microscopy: development and neuroscience applications

© 2017 Elsevier Ltd Many neuroscience questions center around understanding how the molecules and wiring in neural circuits mechanistically yield behavioral functions, or go awry in disease states. However, mapping the molecules and wiring of neurons across the large scales of neural circuits has po...

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Bibliographic Details
Main Authors: Karagiannis, Emmanouil D, Boyden, Edward S
Other Authors: Massachusetts Institute of Technology. Media Laboratory
Format: Article
Language:English
Published: Elsevier BV 2021
Online Access:https://hdl.handle.net/1721.1/134926
Description
Summary:© 2017 Elsevier Ltd Many neuroscience questions center around understanding how the molecules and wiring in neural circuits mechanistically yield behavioral functions, or go awry in disease states. However, mapping the molecules and wiring of neurons across the large scales of neural circuits has posed a great challenge. We recently developed expansion microscopy (ExM), a process in which we physically magnify biological specimens such as brain circuits. We synthesize throughout preserved brain specimens a dense, even mesh of a swellable polymer such as sodium polyacrylate, anchoring key biomolecules such as proteins and nucleic acids to the polymer. After mechanical homogenization of the specimen-polymer composite, we add water, and the polymer swells, pulling biomolecules apart. Due to the larger separation between molecules, ordinary microscopes can then perform nanoscale resolution imaging. We here review the ExM technology as well as applications to the mapping of synapses, cells, and circuits, including deployment in species such as Drosophila, mouse, non-human primate, and human.