Distinct subnetworks of the thalamic reticular nucleus
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nihms-1583670.pdf
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Accepted version
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1.8 MB
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Author(s) • • • • • • • • •
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.
Date Issued
July 2020
Journal
Nature
Publisher
Springer Science and Business Media LLC
Citation
Li, Yinqing et al. "Distinct subnetworks of the thalamic reticular nucleus." Nature 583, 7818 (July 2020): 819–824. © 2020 The Author(s)
Version
Author's final manuscript
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.
MIT Department
McGovern Institute for Brain Research at MIT
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Klarman Cell Observatory (Broad Institute)
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DOI of Published Version
https://doi.org/10.1038/s41586-020-2504-5