Distinct descending motor cortex pathways and their roles in movement
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Abstract
Activity in the motor cortex predicts movements, seconds before they are initiated. This preparatory activity has been observed across cortical layers, including in descending pyramidal tract neurons in layer 5. A key question is how preparatory activity is maintained without causing movement, and is ultimately converted to a motor command to trigger appropriate movements. Here, using single-cell transcriptional profiling and axonal reconstructions, we identify two types of pyramidal tract neuron. Both types project to several targets in the basal ganglia and brainstem. One type projects to thalamic regions that connect back to motor cortex; populations of these neurons produced early preparatory activity that persisted until the movement was initiated. The second type projects to motor centres in the medulla and mainly produced late preparatory activity and motor commands. These results indicate that two types of motor cortex output neurons have specialized roles in motor control.
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The three ALM L5 PT types previously identified correspond to cluster #248 (thalamus-projecting cells) in the Npnt supertype and clusters #249 and #252 (medulla-projecting cells) in the Cdh13 supertype, respectively.
“The three ALM L5 PT types previously identified (Economo et al., 2018; Tasic et al., 2018) correspond to cluster #248 (thalamus-projecting cells) in the Npnt supertype and clusters #249 and #252 (medulla-projecting cells) in the Cdh13 supertype, respectively”
From A taxonomy of transcriptomic cell types across the isocortex and hippocampal formation (2021) · cites this paper as Economo et al., 2018
MY-projecting neurons showed clear enrichment for L5 ET cluster 0.
“MY-projecting neurons showed clear enrichment for L5 ET cluster 0 (Fig. 4e, Extended Data Fig. 3b), in agreement with scRNA-seq data for anterolateral motor cortex (ALM), part of MOs9,53.”
From A multimodal cell census and atlas of the mammalian primary motor cortex (2021) · cites this paper as [53]
Previous studies showed that in mouse ALM, L5 ET neurons have two transcriptomically distinct projection types that may be involved in different motor control functions: TH-projecting type in movement planning and MY-projecting type in movement initiation.
“Previous studies showed that in mouse ALM, L5 ET neurons have two transcriptomically distinct projection types that may be involved in different motor control functions: the TH-projecting type in movement planning and the MY-projecting type in movement initiation53.”
From A multimodal cell census and atlas of the mammalian primary motor cortex (2021) · cites this paper as [53]
Detailed axon projections of MY-projecting and non-MY-projecting L5 ET neurons revealed complex axon collaterals in TH and midbrain regions.
“Confirming and extending previous reports53, we characterized detailed axon projections of the MY-projecting and non-MY-projecting L5 ET neurons, revealing complex axon collaterals in TH and midbrain regions44,46.”
From A multimodal cell census and atlas of the mammalian primary motor cortex (2021) · cites this paper as [53]
This method identified layer 5 pyramidal-tract neuron subpopulations in mouse motor cortex that project to thalamus or medulla and have different motor-control roles.
“This approach helped identify sub-populations of layer 5 pyramidal-tract neurons in the mouse motor cortex with distinct projections in the thalamus and medulla, and different roles in motor control (Economo et al., 2018).”
From Single-Cell Sequencing of Brain Cell Transcriptomes and Epigenomes (2021) · cites this paper as Economo et al., 2018
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Matho, K. S., Huilgol, D., Galbavy, W., He, M., Kim, G., An, X., Lu, J., Wu, P., Di Bella, D. J., Shetty, A. S., et al. (2020) · doi:10.1101/2020.04.22.054064 · Cited by 20 · see citing works
Epigenomic Diversity of Cortical Projection Neurons in the Mouse Brain
Zhang, Z., Zhou, J., Tan, P., Pang, Y., Rivkin, A., Kirchgessner, M. A., Williams, E., Lee, C.-T., Liu, H., Franklin, A. D., et al. (2020) · doi:10.1101/2020.04.01.019612 · Cited by 75 · see citing works
- Authors
- Economo, M. N., Viswanathan, S., Tasic, B., Bas, E., Winnubst, J., Menon, V., Graybuck, L. T., Nguyen, T. N., Smith, K. A., Yao, Z., Wang, L., Gerfen, C. R., Chandrashekar, J., Zeng, H., Looger, L. L., & Svoboda, K.
- Affiliations
- Howard Hughes Medical Institute (US)
- Allen Institute for Brain Science (US)
- National Institute of Mental Health (US)
- Corresponding author
- Svoboda, Karel
- ORCID
- Venue
- Nature
- Published
- 2018-10-31
- Volume
- 563
- Issue
- 7729
- Pages
- 79-84
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2781822280
- Cited by
- 415
- References
- 53
- Citations by year
- 2026: 39 · 2025: 41 · 2024: 43 · 2023: 60 · 2022: 53 · 2021: 72 · 2020: 56 · 2019: 43 · 2018: 7 · 2017: 1
- FWCI
- 26.52
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of Mental Health (ZIAMH002497)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Motor Control and Adaptation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- motor cortex, pyramidal tract neurons, layer 5, motor preparation, basal ganglia, brainstem, thalamus, medulla, axonal projections, motor command, descending motor pathways
- MeSH terms
- Animals, Basal Ganglia, Brain Stem, Efferent Pathways, Medulla Oblongata, Motor Cortex, Movement, Neurons, Pyramidal Cells, Glutamic Acid, Mice, Single-Cell Analysis, Transcriptome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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