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      The mouse cortico–basal ganglia–thalamic network

      research-article
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      Nature
      Nature Publishing Group UK
      Network models, Basal ganglia, Neural circuits, Single-cell imaging, Brain

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          Abstract

          The cortico–basal ganglia–thalamo–cortical loop is one of the fundamental network motifs in the brain. Revealing its structural and functional organization is critical to understanding cognition, sensorimotor behaviour, and the natural history of many neurological and neuropsychiatric disorders. Classically, this network is conceptualized to contain three information channels: motor, limbic and associative 14 . Yet this three-channel view cannot explain the myriad functions of the basal ganglia. We previously subdivided the dorsal striatum into 29 functional domains on the basis of the topography of inputs from the entire cortex 5 . Here we map the multi-synaptic output pathways of these striatal domains through the globus pallidus external part (GPe), substantia nigra reticular part (SNr), thalamic nuclei and cortex. Accordingly, we identify 14 SNr and 36 GPe domains and a direct cortico-SNr projection. The striatonigral direct pathway displays a greater convergence of striatal inputs than the more parallel striatopallidal indirect pathway, although direct and indirect pathways originating from the same striatal domain ultimately converge onto the same postsynaptic SNr neurons. Following the SNr outputs, we delineate six domains in the parafascicular and ventromedial thalamic nuclei. Subsequently, we identify six parallel cortico–basal ganglia–thalamic subnetworks that sequentially transduce specific subsets of cortical information through every elemental node of the cortico–basal ganglia–thalamic loop. Thalamic domains relay this output back to the originating corticostriatal neurons of each subnetwork in a bona fide closed loop.

          Abstract

          Mesoscale connectomic mapping of the cortico–basal ganglia–thalamic network reveals key architectural and information processing features.

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          Most cited references64

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          Fast unfolding of communities in large networks

          Journal of Statistical Mechanics: Theory and Experiment, 2008(10), P10008
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            Parallel organization of functionally segregated circuits linking basal ganglia and cortex.

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              A mesoscale connectome of the mouse brain.

              Comprehensive knowledge of the brain's wiring diagram is fundamental for understanding how the nervous system processes information at both local and global scales. However, with the singular exception of the C. elegans microscale connectome, there are no complete connectivity data sets in other species. Here we report a brain-wide, cellular-level, mesoscale connectome for the mouse. The Allen Mouse Brain Connectivity Atlas uses enhanced green fluorescent protein (EGFP)-expressing adeno-associated viral vectors to trace axonal projections from defined regions and cell types, and high-throughput serial two-photon tomography to image the EGFP-labelled axons throughout the brain. This systematic and standardized approach allows spatial registration of individual experiments into a common three dimensional (3D) reference space, resulting in a whole-brain connectivity matrix. A computational model yields insights into connectional strength distribution, symmetry and other network properties. Virtual tractography illustrates 3D topography among interconnected regions. Cortico-thalamic pathway analysis demonstrates segregation and integration of parallel pathways. The Allen Mouse Brain Connectivity Atlas is a freely available, foundational resource for structural and functional investigations into the neural circuits that support behavioural and cognitive processes in health and disease.
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                Author and article information

                Contributors
                nnfoster@mednet.ucla.edu
                HongWeiD@mednet.ucla.edu
                Journal
                Nature
                Nature
                Nature
                Nature Publishing Group UK (London )
                0028-0836
                1476-4687
                6 October 2021
                6 October 2021
                2021
                : 598
                : 7879
                : 188-194
                Affiliations
                [1 ]GRID grid.19006.3e, ISNI 0000 0000 9632 6718, UCLA Brain Research and Artificial Intelligence Nexus, Department of Neurobiology, , David Geffen School of Medicine at UCLA, ; Los Angeles, CA USA
                [2 ]GRID grid.42505.36, ISNI 0000 0001 2156 6853, Mark and Mary Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine, , University of Southern California, ; Los Angeles, CA USA
                [3 ]GRID grid.19006.3e, ISNI 0000 0000 9632 6718, Jane and Terry Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, , David Geffen School of Medicine at UCLA, ; Los Angeles, CA USA
                [4 ]GRID grid.42505.36, ISNI 0000 0001 2156 6853, Zilkha Neurogenetic Institute, Keck School of Medicine, , University of Southern California, ; Los Angeles, CA USA
                [5 ]GRID grid.33199.31, ISNI 0000 0004 0368 7223, Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, MoE Key Laboratory for Biomedical Photonics, School of Engineering Sciences, , Huazhong University of Science and Technology, ; Wuhan, China
                [6 ]GRID grid.263761.7, ISNI 0000 0001 0198 0694, HUST-Suzhou Institute for Brainsmatics, , JITRI Institute for Brainsmatics, ; Suzhou, China
                [7 ]GRID grid.266100.3, ISNI 0000 0001 2107 4242, Neurobiology Section, Division of Biological Sciences, , University of California, San Diego, ; La Jolla, CA USA
                [8 ]GRID grid.9227.e, ISNI 0000000119573309, CAS Center for Excellence in Brain Science and Intelligence Technology, , Chinese Academy of Science, ; Shanghai, China
                [9 ]Center for Neurobehavioral Genetics, Jane and Terry Semel Institute for Neuroscience, Los Angeles, CA USA
                [10 ]GRID grid.116068.8, ISNI 0000 0001 2341 2786, McGovern Institute for Brain Research, , Massachusetts Institute of Technology, ; Cambridge, MA USA
                [11 ]GRID grid.428986.9, ISNI 0000 0001 0373 6302, School of Biomedical Engineering, , Hainan University, ; Haikou, China
                [12 ]GRID grid.42505.36, ISNI 0000 0001 2156 6853, Department of Biological Sciences, , University of Southern California, ; Los Angeles, CA USA
                Author information
                http://orcid.org/0000-0003-1740-9788
                http://orcid.org/0000-0001-6963-1247
                http://orcid.org/0000-0001-8122-189X
                http://orcid.org/0000-0002-3747-2824
                http://orcid.org/0000-0002-5516-8607
                http://orcid.org/0000-0002-1221-6357
                http://orcid.org/0000-0001-5035-7655
                http://orcid.org/0000-0002-7754-0991
                http://orcid.org/0000-0002-8231-8893
                http://orcid.org/0000-0003-3705-7935
                http://orcid.org/0000-0001-5519-6248
                http://orcid.org/0000-0003-0389-5324
                http://orcid.org/0000-0002-6725-9311
                http://orcid.org/0000-0002-3766-5415
                http://orcid.org/0000-0001-9972-3177
                Article
                3993
                10.1038/s41586-021-03993-3
                8494639
                34616074
                18c082bf-c854-40f1-a642-d55d88bfb6da
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 11 June 2020
                : 3 September 2021
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                © The Author(s), under exclusive licence to Springer Nature Limited 2021

                Uncategorized
                network models,basal ganglia,neural circuits,single-cell imaging,brain
                Uncategorized
                network models, basal ganglia, neural circuits, single-cell imaging, brain

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