Distinct subnetworks of the thalamic reticular nucleus
The thalamic reticular nucleus (TRN), the major source of thalamic inhibition, regulates thalamocortical interactions that are critical for sensory processing, attention and cognition1–5. TRN dysfunction has been linked to sensory abnormality, attention deficit and sleep disturbance across multiple...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| 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/1721.1/130405 |
| _version_ | 1826191109629411328 |
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| author | Li, Yinqing Lopez Huerta, Violeta Adiconis, Xian Levandowski, Kirsten Choi, Soonwook Simmons, Sean K. Arias-Garcia, Mario A. Guo, Baolin Yao, Annie Blosser, Timothy R. Wimmer, Ralf D Aida, Tomomi Atamian, Alexander Naik, Tina Sun, Xuyun Bi, Dasheng Malhotra, Diya Hession, Cynthia C. Shema Tirosh, Reut Gomes, Marcos Li, Taibo Hwang, Eunjin Krol, Alexandra Kowalczyk, Monika Peça, João Pan, Gang Halassa, Michael Levin, Joshua Z. Fu, Zhanyan Feng, Guoping |
| author2 | McGovern Institute for Brain Research at MIT |
| author_facet | McGovern Institute for Brain Research at MIT Li, Yinqing Lopez Huerta, Violeta Adiconis, Xian Levandowski, Kirsten Choi, Soonwook Simmons, Sean K. Arias-Garcia, Mario A. Guo, Baolin Yao, Annie Blosser, Timothy R. Wimmer, Ralf D Aida, Tomomi Atamian, Alexander Naik, Tina Sun, Xuyun Bi, Dasheng Malhotra, Diya Hession, Cynthia C. Shema Tirosh, Reut Gomes, Marcos Li, Taibo Hwang, Eunjin Krol, Alexandra Kowalczyk, Monika Peça, João Pan, Gang Halassa, Michael Levin, Joshua Z. Fu, Zhanyan Feng, Guoping |
| author_sort | Li, Yinqing |
| collection | MIT |
| description | The thalamic reticular nucleus (TRN), the major source of thalamic inhibition, regulates thalamocortical interactions that are critical for sensory processing, attention and cognition1–5. TRN dysfunction has been linked to sensory abnormality, attention deficit and sleep disturbance across multiple neurodevelopmental disorders6–9. However, little is known about the organizational principles that underlie its divergent functions. Here we performed an integrative study linking single-cell molecular and electrophysiological features of the mouse TRN to connectivity and systems-level function. We found that cellular heterogeneity in the TRN is characterized by a transcriptomic gradient of two negatively correlated gene-expression profiles, each containing hundreds of genes. Neurons in the extremes of this transcriptomic gradient express mutually exclusive markers, exhibit core or shell-like anatomical structure and have distinct electrophysiological properties. The two TRN subpopulations make differential connections with the functionally distinct first-order and higher-order thalamic nuclei to form molecularly defined TRN–thalamus subnetworks. Selective perturbation of the two subnetworks in vivo revealed their differential role in regulating sleep. In sum, our study provides a comprehensive atlas of TRN neurons at single-cell resolution and links molecularly defined subnetworks to the functional organization of thalamocortical circuits. |
| first_indexed | 2024-09-23T08:50:21Z |
| format | Article |
| id | mit-1721.1/130405 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T08:50:21Z |
| publishDate | 2021 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1304052022-09-23T14:54:25Z Distinct subnetworks of the thalamic reticular nucleus Li, Yinqing Lopez Huerta, Violeta Adiconis, Xian Levandowski, Kirsten Choi, Soonwook Simmons, Sean K. Arias-Garcia, Mario A. Guo, Baolin Yao, Annie Blosser, Timothy R. Wimmer, Ralf D Aida, Tomomi Atamian, Alexander Naik, Tina Sun, Xuyun Bi, Dasheng Malhotra, Diya Hession, Cynthia C. Shema Tirosh, Reut Gomes, Marcos Li, Taibo Hwang, Eunjin Krol, Alexandra Kowalczyk, Monika Peça, João Pan, Gang Halassa, Michael Levin, Joshua Z. Fu, Zhanyan Feng, Guoping McGovern Institute for Brain Research at MIT Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Klarman Cell Observatory (Broad Institute) The thalamic reticular nucleus (TRN), the major source of thalamic inhibition, regulates thalamocortical interactions that are critical for sensory processing, attention and cognition1–5. TRN dysfunction has been linked to sensory abnormality, attention deficit and sleep disturbance across multiple neurodevelopmental disorders6–9. However, little is known about the organizational principles that underlie its divergent functions. Here we performed an integrative study linking single-cell molecular and electrophysiological features of the mouse TRN to connectivity and systems-level function. We found that cellular heterogeneity in the TRN is characterized by a transcriptomic gradient of two negatively correlated gene-expression profiles, each containing hundreds of genes. Neurons in the extremes of this transcriptomic gradient express mutually exclusive markers, exhibit core or shell-like anatomical structure and have distinct electrophysiological properties. The two TRN subpopulations make differential connections with the functionally distinct first-order and higher-order thalamic nuclei to form molecularly defined TRN–thalamus subnetworks. Selective perturbation of the two subnetworks in vivo revealed their differential role in regulating sleep. In sum, our study provides a comprehensive atlas of TRN neurons at single-cell resolution and links molecularly defined subnetworks to the functional organization of thalamocortical circuits. NIH/NIMH (Grants R01NS098505, R01NS113245) NIH (Grants R01NS098505, R01MH107680) 2021-04-07T21:02:09Z 2021-04-07T21:02:09Z 2020-07 2019-05 2021-04-06T18:50:09Z Article http://purl.org/eprint/type/JournalArticle 0028-0836 1476-4687 https://hdl.handle.net/1721.1/130405 Li, Yinqing et al. "Distinct subnetworks of the thalamic reticular nucleus." Nature 583, 7818 (July 2020): 819–824. © 2020 The Author(s) en http://dx.doi.org/10.1038/s41586-020-2504-5 Nature Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Springer Science and Business Media LLC PMC |
| spellingShingle | Li, Yinqing Lopez Huerta, Violeta Adiconis, Xian Levandowski, Kirsten Choi, Soonwook Simmons, Sean K. Arias-Garcia, Mario A. Guo, Baolin Yao, Annie Blosser, Timothy R. Wimmer, Ralf D Aida, Tomomi Atamian, Alexander Naik, Tina Sun, Xuyun Bi, Dasheng Malhotra, Diya Hession, Cynthia C. Shema Tirosh, Reut Gomes, Marcos Li, Taibo Hwang, Eunjin Krol, Alexandra Kowalczyk, Monika Peça, João Pan, Gang Halassa, Michael Levin, Joshua Z. Fu, Zhanyan Feng, Guoping Distinct subnetworks of the thalamic reticular nucleus |
| title | Distinct subnetworks of the thalamic reticular nucleus |
| title_full | Distinct subnetworks of the thalamic reticular nucleus |
| title_fullStr | Distinct subnetworks of the thalamic reticular nucleus |
| title_full_unstemmed | Distinct subnetworks of the thalamic reticular nucleus |
| title_short | Distinct subnetworks of the thalamic reticular nucleus |
| title_sort | distinct subnetworks of the thalamic reticular nucleus |
| url | https://hdl.handle.net/1721.1/130405 |
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