AAVs of CMV-Cre and Cre-dependent EF1a-DIO-GFP were used for sparse labelling of striatal neurons. (From
BrainVTA)
The viruses used in this article are in the table below
|
Control |
PT-0258 rAAV-EFlα-DIO-GFP |
|
CRE Recombinase |
PT-0025 rAAV-CMV-Cre |
Nicholas N Foster, Joshua Barry, Laura Korobkova, Luis Garcia, Lei Gao, Marlene Becerra, Yasmine Sherafat, Bo Peng, Xiangning Li, Jun-Hyeok Choi, Lin Gou, Brian Zingg, Sana Azam, Darrick Lo, Neda Khanjani, Bin Zhang, Jim Stanis, Ian Bowman, Kaelan Cotter, Chunru Cao, Seita Yamashita, Amanda Tugangui, Anan Li, Tao Jiang, Xueyan Jia, Zhao Feng, Sarvia Aquino, Hyun-Seung Mun, Muye Zhu, Anthony Santarelli, Nora L Benavidez, Monica Song, Gordon Dan, Marina Fayzullina, Sarah Ustrell, Tyler Boesen, David L Johnson, Hanpeng Xu, Michael S Bienkowski, X William Yang, Hui Gong, Michael S Levine, Ian Wickersham, Qingming Luo, Joel D Hahn, Byung Kook Lim, Li I Zhang, Carlos Cepeda, Houri Hintiryan, Hong-Wei Dong
Pub Date: 2021-10-06,
DOI: 10.1038/s41586-021-03993-3,
Email: [email protected]
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 associative1,2,3,4. 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 cortex5. 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.
Figure 1. Demonstration of the oro-brachial subnetwork loop.
In this study, this work reveals that the canonical cortico–basal ganglia–thalamic network is composed of six parallel subnetworks, each of which is organized by a number of nodes that are precisely and richly interconnected.
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