Abstract
The basal ganglia are essential for executing motor actions. How the basal ganglia engage spinal motor networks has remained elusive. Medullary Chx10 gigantocellular (Gi) neurons are required for turning gait programs, suggesting that turning gaits organized by the basal ganglia are executed via this descending pathway. Performing deep brainstem recordings of Chx10 Gi Ca2+ activity in adult mice, we show that striatal projection neurons initiate turning gaits via a dominant crossed pathway to Chx10 Gi neurons on the contralateral side. Using intersectional viral tracing and cell-type-specific modulation, we uncover the principal basal ganglia–spinal cord pathway for locomotor asymmetries in mice: basal ganglia → pontine reticular nucleus, oral part (PnO) → Chx10 Gi → spinal cord. Modulating the restricted PnO → Chx10 Gi pathway restores turning competence upon striatal damage, suggesting that dysfunction of this pathway may contribute to debilitating turning deficits observed in Parkinson’s disease. Our results reveal the stratified circuit architecture underlying a critical motor program.
Originalsprog | Engelsk |
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Tidsskrift | Nature Neuroscience |
Vol/bind | 27 |
Sider (fra-til) | 716–727 |
Antal sider | 12 |
ISSN | 1097-6256 |
DOI | |
Status | Udgivet - 2024 |
Bibliografisk note
Funding Information:We thank K. Sharma, L. Zagoraiou, S. Crone and T. M. Jessell for the Chx10 mouse. Imaging was performed in the Core Facility for Integrated Microscopy, Faculty of Health and Medical Sciences, University of Copenhagen. We thank I. Vesth-Hansen, I. Allodi, M. Aagaard Andersen, I. Mustafic and M. Lønstrup for technical and administrative assistance, and members of O.K.’s laboratory for discussion and comments on previous versions of this paper. This work was supported by the Lundbeck Foundation (grant no. R347-2020-2393) to J.M.C.; the Danish Society for Neuroscience-Lundbeck Foundation Scholarstipend and the Neuroscience Academy Denmark to S.K.S.; and the Novo Nordisk Laureate Program (grant no. NNF15OC0014186), the Lundbeck Foundation (grant nos. R276-2018-183 and R345-2020-1769) and the Independent Research Fund Denmark (grant no. 9039-00034B) to O.K. Cre
Publisher Copyright:
© The Author(s) 2024.