4.7 Article

Multi-scale light microscopy/electron microscopy neuronal imaging from brain to synapse with a tissue clearing method, ScaleSF

期刊

ISCIENCE
卷 25, 期 1, 页码 -

出版社

CELL PRESS
DOI: 10.1016/j.isci.2021.103601

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资金

  1. Japan Society for the Promotion of Science (JSPS) [JP21H03529, JP20K07231, JP20K07743, JP21H02592, JP18H04743]
  2. Japan Agency for Medical Research and Development (AMED) [JP21dm0207112, JP19dm0207093, JP18dm0207020]
  3. Moonshot R&D from the Japan Science and Technology Agency (JST) [JPMJMS2024]
  4. Fusion Oriented Research for disruptive Science and Technology (FOREST) from JST [JPMJFR204D]
  5. Research Institute for Diseases of Old Age at the Juntendo University School of Medicine [X2016, X2001]
  6. Private School Branding Project

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Multi-scale neuronal imaging technique combines different imaging methods and tissue clearing methods to enable observation and analysis of neural circuits at different scales, helping us better understand the brain's connectivity.
The mammalian brain is organized over sizes that span several orders of magnitude, from synapses to the entire brain. Thus, a technique to visualize neural circuits across multiple spatial scales (multi-scale neuronal imaging) is vital for deciphering brain-wide connectivity. Here, we developed this technique by coupling successive light microscopy/electron microscopy (LM/EM) imaging with a glutaraldehyde-resistant tissue clearing method, ScaleSF. Our multi-scale neuronal imaging incorporates (1) brain-wide macroscopic observation, (2) mesoscopic circuit mapping, (3) microscopic subcellular imaging, and (4) EM imaging of nanoscopic structures, allowing seamless integration of structural information from the brain to synapses. We applied this technique to three neural circuits of two different species, mouse striatofugal, mouse callosal, and marmoset corti-costriatal projection systems, and succeeded in simultaneous interrogation of their circuit structure and synaptic connectivity in a targeted way. Our multi-scale neuronal imaging will Significantly advance the understanding of brain-wide connectivity by expanding the scales of objects.

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