Light microscopy based approach for mapping connectivity with molecular specificity
© 2020, The Author(s). 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 spec...
| Main Authors: | , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
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Springer Science and Business Media LLC
2021
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| Online Access: | https://hdl.handle.net/1721.1/135429 |
| _version_ | 1826201723566292992 |
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| author | Shen, Fred Y Harrington, Margaret M Walker, Logan A Cheng, Hon Pong Jimmy Boyden, Edward S Cai, Dawen |
| author2 | McGovern Institute for Brain Research at MIT |
| author_facet | McGovern Institute for Brain Research at MIT Shen, Fred Y Harrington, Margaret M Walker, Logan A Cheng, Hon Pong Jimmy Boyden, Edward S Cai, Dawen |
| author_sort | Shen, Fred Y |
| collection | MIT |
| description | © 2020, The Author(s). 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. |
| first_indexed | 2024-09-23T11:55:44Z |
| format | Article |
| id | mit-1721.1/135429 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T11:55:44Z |
| publishDate | 2021 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1354292023-09-15T19:30:43Z Light microscopy based approach for mapping connectivity with molecular specificity Shen, Fred Y Harrington, Margaret M Walker, Logan A Cheng, Hon Pong Jimmy Boyden, Edward S Cai, Dawen McGovern Institute for Brain Research at MIT Koch Institute for Integrative Cancer Research at MIT Program in Media Arts and Sciences (Massachusetts Institute of Technology) Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Howard Hughes Medical Institute © 2020, The Author(s). 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. 2021-10-27T20:23:26Z 2021-10-27T20:23:26Z 2020 2021-03-23T17:20:35Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/135429 en 10.1038/S41467-020-18422-8 Nature Communications Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Springer Science and Business Media LLC Nature |
| spellingShingle | Shen, Fred Y Harrington, Margaret M Walker, Logan A Cheng, Hon Pong Jimmy Boyden, Edward S Cai, Dawen Light microscopy based approach for mapping connectivity with molecular specificity |
| title | Light microscopy based approach for mapping connectivity with molecular specificity |
| title_full | Light microscopy based approach for mapping connectivity with molecular specificity |
| title_fullStr | Light microscopy based approach for mapping connectivity with molecular specificity |
| title_full_unstemmed | Light microscopy based approach for mapping connectivity with molecular specificity |
| title_short | Light microscopy based approach for mapping connectivity with molecular specificity |
| title_sort | light microscopy based approach for mapping connectivity with molecular specificity |
| url | https://hdl.handle.net/1721.1/135429 |
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