Distinct subnetworks of the thalamic reticular nucleus

Yinqing Li, Violeta G. Lopez-Huerta, Xian Adiconis, Kirsten Levandowski, Soonwook Choi, Sean K. Simmons, Mario A. Arias-Garcia, Baolin Guo, Annie Y. Yao, Timothy R. Blosser, Ralf D. Wimmer, Tomomi Aida, Alexander Atamian, Tina Naik, Xuyun Sun, Dasheng Bi, Diya Malhotra, Cynthia C. Hession, Reut Shema, Marcos Gomes, Taibo Li, Eunjin Hwang, Alexandra Krol, Monika Kowalczyk, João Peça, Gang Pan, Michael M. Halassa, Joshua Z. Levin (), Zhanyan Fu () and Guoping Feng ()
Additional contact information
Yinqing Li: Tsinghua University
Violeta G. Lopez-Huerta: Broad Institute of MIT and Harvard
Xian Adiconis: Broad Institute of MIT and Harvard
Kirsten Levandowski: Broad Institute of MIT and Harvard
Soonwook Choi: Broad Institute of MIT and Harvard
Sean K. Simmons: Broad Institute of MIT and Harvard
Mario A. Arias-Garcia: Broad Institute of MIT and Harvard
Baolin Guo: Broad Institute of MIT and Harvard
Annie Y. Yao: Broad Institute of MIT and Harvard
Timothy R. Blosser: Broad Institute of MIT and Harvard
Ralf D. Wimmer: Massachusetts Institute of Technology
Tomomi Aida: Broad Institute of MIT and Harvard
Alexander Atamian: Broad Institute of MIT and Harvard
Tina Naik: Broad Institute of MIT and Harvard
Xuyun Sun: Massachusetts Institute of Technology
Dasheng Bi: Massachusetts Institute of Technology
Diya Malhotra: Broad Institute of MIT and Harvard
Cynthia C. Hession: Broad Institute of MIT and Harvard
Reut Shema: Broad Institute of MIT and Harvard
Marcos Gomes: Massachusetts Institute of Technology
Taibo Li: Broad Institute of MIT and Harvard
Eunjin Hwang: Korea Institute of Science and Technology
Alexandra Krol: Massachusetts Institute of Technology
Monika Kowalczyk: Broad Institute of MIT and Harvard
João Peça: Center for Neuroscience and Cell Biology
Gang Pan: Zhejiang University
Michael M. Halassa: Massachusetts Institute of Technology
Joshua Z. Levin: Broad Institute of MIT and Harvard
Zhanyan Fu: Broad Institute of MIT and Harvard
Guoping Feng: Broad Institute of MIT and Harvard

Nature, 2020, vol. 583, issue 7818, 819-824

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41586-020-2504-5

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