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Publication : Light microscopy based approach for mapping connectivity with molecular specificity.

First Author  Shen FY Year  2020
Journal  Nat Commun Volume  11
Issue  1 Pages  4632
PubMed ID  32934230 Mgi Jnum  J:358696
Mgi Id  MGI:6470510 Doi  10.1038/s41467-020-18422-8
Citation  Shen FY, et al. (2020) Light microscopy based approach for mapping connectivity with molecular specificity. Nat Commun 11(1):4632
abstractText  Mapping neuroanatomy is a foundational goal towards understanding brain function. Electron microscopy (EM) has been the gold standard for connectivity analysis because nanoscale resolution is necessary to unambiguously resolve synapses. However, molecular information that specifies cell types is often lost in EM reconstructions. To address this, we devise a light microscopy approach for connectivity analysis of defined cell types called spectral connectomics. We combine multicolor labeling (Brainbow) of neurons with multi-round immunostaining Expansion Microscopy (miriEx) to simultaneously interrogate morphology, molecular markers, and connectivity in the same brain section. We apply this strategy to directly link inhibitory neuron cell types with their morphologies. Furthermore, we show that correlative Brainbow and endogenous synaptic machinery immunostaining can define putative synaptic connections between neurons, as well as map putative inhibitory and excitatory inputs. We envision that spectral connectomics can be applied routinely in neurobiology labs to gain insights into normal and pathophysiological neuroanatomy.
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