Rapid reconstruction of neural circuits using tissue expansion and light sheet microscopy
<jats:p>Brain function is mediated by the physiological coordination of a vast, intricately connected network of molecular and cellular components. The physiological properties of neural network components can be quantified with high throughput. The ability to assess many animals per study has...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications, Ltd
2023
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| Online Access: | https://hdl.handle.net/1721.1/148691 |
| _version_ | 1811072120307843072 |
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| author | Lillvis, Joshua L Otsuna, Hideo Ding, Xiaoyu Pisarev, Igor Kawase, Takashi Colonell, Jennifer Rokicki, Konrad Goina, Cristian Gao, Ruixuan Hu, Amy Wang, Kaiyu Bogovic, John Milkie, Daniel E Meienberg, Linus Mensh, Brett D Boyden, Edward S Saalfeld, Stephan Tillberg, Paul W Dickson, Barry J |
| author2 | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Lillvis, Joshua L Otsuna, Hideo Ding, Xiaoyu Pisarev, Igor Kawase, Takashi Colonell, Jennifer Rokicki, Konrad Goina, Cristian Gao, Ruixuan Hu, Amy Wang, Kaiyu Bogovic, John Milkie, Daniel E Meienberg, Linus Mensh, Brett D Boyden, Edward S Saalfeld, Stephan Tillberg, Paul W Dickson, Barry J |
| author_sort | Lillvis, Joshua L |
| collection | MIT |
| description | <jats:p>Brain function is mediated by the physiological coordination of a vast, intricately connected network of molecular and cellular components. The physiological properties of neural network components can be quantified with high throughput. The ability to assess many animals per study has been critical in relating physiological properties to behavior. By contrast, the synaptic structure of neural circuits is presently quantifiable only with low throughput. This low throughput hampers efforts to understand how variations in network structure relate to variations in behavior. For neuroanatomical reconstruction, there is a methodological gulf between electron microscopic (EM) methods, which yield dense connectomes at considerable expense and low throughput, and light microscopic (LM) methods, which provide molecular and cell-type specificity at high throughput but without synaptic resolution. To bridge this gulf, we developed a high-throughput analysis pipeline and imaging protocol using tissue expansion and light sheet microscopy (ExLLSM) to rapidly reconstruct selected circuits across many animals with single-synapse resolution and molecular contrast. Using <jats:italic>Drosophila</jats:italic> to validate this approach, we demonstrate that it yields synaptic counts similar to those obtained by EM, enables synaptic connectivity to be compared across sex and experience, and can be used to correlate structural connectivity, functional connectivity, and behavior. This approach fills a critical methodological gap in studying variability in the structure and function of neural circuits across individuals within and between species.</jats:p> |
| first_indexed | 2024-09-23T09:01:13Z |
| format | Article |
| id | mit-1721.1/148691 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T09:01:13Z |
| publishDate | 2023 |
| publisher | eLife Sciences Publications, Ltd |
| record_format | dspace |
| spelling | mit-1721.1/1486912023-03-25T03:46:52Z Rapid reconstruction of neural circuits using tissue expansion and light sheet microscopy Lillvis, Joshua L Otsuna, Hideo Ding, Xiaoyu Pisarev, Igor Kawase, Takashi Colonell, Jennifer Rokicki, Konrad Goina, Cristian Gao, Ruixuan Hu, Amy Wang, Kaiyu Bogovic, John Milkie, Daniel E Meienberg, Linus Mensh, Brett D Boyden, Edward S Saalfeld, Stephan Tillberg, Paul W Dickson, Barry J Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences <jats:p>Brain function is mediated by the physiological coordination of a vast, intricately connected network of molecular and cellular components. The physiological properties of neural network components can be quantified with high throughput. The ability to assess many animals per study has been critical in relating physiological properties to behavior. By contrast, the synaptic structure of neural circuits is presently quantifiable only with low throughput. This low throughput hampers efforts to understand how variations in network structure relate to variations in behavior. For neuroanatomical reconstruction, there is a methodological gulf between electron microscopic (EM) methods, which yield dense connectomes at considerable expense and low throughput, and light microscopic (LM) methods, which provide molecular and cell-type specificity at high throughput but without synaptic resolution. To bridge this gulf, we developed a high-throughput analysis pipeline and imaging protocol using tissue expansion and light sheet microscopy (ExLLSM) to rapidly reconstruct selected circuits across many animals with single-synapse resolution and molecular contrast. Using <jats:italic>Drosophila</jats:italic> to validate this approach, we demonstrate that it yields synaptic counts similar to those obtained by EM, enables synaptic connectivity to be compared across sex and experience, and can be used to correlate structural connectivity, functional connectivity, and behavior. This approach fills a critical methodological gap in studying variability in the structure and function of neural circuits across individuals within and between species.</jats:p> 2023-03-24T12:10:36Z 2023-03-24T12:10:36Z 2022 2023-03-24T12:02:52Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/148691 Lillvis, Joshua L, Otsuna, Hideo, Ding, Xiaoyu, Pisarev, Igor, Kawase, Takashi et al. 2022. "Rapid reconstruction of neural circuits using tissue expansion and light sheet microscopy." eLife, 11. en 10.7554/ELIFE.81248 eLife Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf eLife Sciences Publications, Ltd eLife |
| spellingShingle | Lillvis, Joshua L Otsuna, Hideo Ding, Xiaoyu Pisarev, Igor Kawase, Takashi Colonell, Jennifer Rokicki, Konrad Goina, Cristian Gao, Ruixuan Hu, Amy Wang, Kaiyu Bogovic, John Milkie, Daniel E Meienberg, Linus Mensh, Brett D Boyden, Edward S Saalfeld, Stephan Tillberg, Paul W Dickson, Barry J Rapid reconstruction of neural circuits using tissue expansion and light sheet microscopy |
| title | Rapid reconstruction of neural circuits using tissue expansion and light sheet microscopy |
| title_full | Rapid reconstruction of neural circuits using tissue expansion and light sheet microscopy |
| title_fullStr | Rapid reconstruction of neural circuits using tissue expansion and light sheet microscopy |
| title_full_unstemmed | Rapid reconstruction of neural circuits using tissue expansion and light sheet microscopy |
| title_short | Rapid reconstruction of neural circuits using tissue expansion and light sheet microscopy |
| title_sort | rapid reconstruction of neural circuits using tissue expansion and light sheet microscopy |
| url | https://hdl.handle.net/1721.1/148691 |
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