Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Sensory cortical control of movement

Nature Neuroscience volume 23, pages 75–84 (2020)Cite this article

Subjects

Abstract

Walking in our complex environment requires continual higher order integrated spatiotemporal information. This information is processed in the somatosensory cortex, and it has long been presumed that it influences movement via descending tracts originating from the motor cortex. Here we show that neuronal activity in the primary somatosensory cortex tightly correlates with the onset and speed of locomotion in freely moving mice. Using optogenetics and pharmacogenetics in combination with in vivo and in vitro electrophysiology, we provide evidence for a direct corticospinal pathway from the primary somatosensory cortex that synapses with cervical excitatory neurons and modulates the lumbar locomotor network independently of the motor cortex and other supraspinal locomotor centers. Stimulation of this pathway enhances speed of locomotion, while inhibition decreases locomotor speed and ultimately terminates stepping. Our findings reveal a novel pathway for neural control of movement whereby the somatosensory cortex directly influences motor behavior, possibly in response to environmental cues.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Electrophysiological recording of somatosensory activity in freely behaving mice.
Fig. 2: Photostimulation of SI pyramidal neurons induces activity in the lumbar cord.
Fig. 3: Somatosensory cortical connectivity and lumbar spinal cord.
Fig. 4: The sensory cortex increased the frequency of locomotor-like activity in vitro via cervical excitatory neurotransmission.
Fig. 5: Sensory cortex regulates locomotor output.
Fig. 6: The sensory cortical pathway is necessary for maintenance of locomotion.
Fig. 7: Cervical eINs relay the SI motor signal to the lumbar spinal cord.
Fig. 8: Cervical excitatory cells project predominantly to lamina VII of the upper lumbar spinal cord.

Data availability

Source data have been provided for Figs. 1c,d (values in Fig. 1d are the square root of values in Fig. 1c), 2d,e, 4c, 5c,e, 6a,b and 7c. Source data have also been provided for Extended Data Figs. 2b, 5a–c,e, 6, 7a,b and 8. Any additional data pertaining to this manuscript is available from the authors upon reasonable request.

Code availability

Any custom script or code used in this study is available from the authors upon reasonable request.

References

  1. Andersson, O., Forssberg, H., Grillner, S. & Wallen, P. Peripheral feedback mechanisms acting on the central pattern generators for locomotion in fish and cat. Can. J. Physiol. Pharmacol. 59, 713–726 (1981).

    CAS  PubMed  Google Scholar 

  2. Kiehn, O. Locomotor circuits in the mammalian spinal cord. Annu. Rev. Neurosci. 29, 279–306 (2006).

    CAS  PubMed  Google Scholar 

  3. Kiehn, O. Decoding the organization of spinal circuits that control locomotion. Nat. Rev. Neurosci. 17, 224–238 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Kjaerulff, O. & Kiehn, O. Distribution of networks generating and coordinating locomotor activity in the neonatal rat spinal cord in vitro: a lesion study. J. Neurosci. 16, 5777–5794 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Drew, T. Motor cortical activity during voluntary gait modifications in the cat. I. Cells related to the forelimbs. J. Neurophysiol. 70, 179–199 (1993).

    CAS  PubMed  Google Scholar 

  6. Garcia-Rill, E. & Skinner, R. D. The mesencephalic locomotor region. I. Activation of a medullary projection site. Brain Res. 411, 1–12 (1987).

    CAS  PubMed  Google Scholar 

  7. Hagglund, M., Borgius, L., Dougherty, K. J. & Kiehn, O. Activation of groups of excitatory neurons in the mammalian spinal cord or hindbrain evokes locomotion. Nat. Neurosci. 13, 246–252 (2010).

    PubMed  Google Scholar 

  8. Jankowska, E., Nilsson, E. & Hammar, I. Processing information related to centrally initiated locomotor and voluntary movements by feline spinocerebellar neurones. J. Physiol. 589, 5709–5725 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Matsuyama, K. et al. Locomotor role of the corticoreticular–reticulospinal–spinal interneuronal system. Prog. Brain Res. 143, 239–249 (2004).

    PubMed  Google Scholar 

  10. Shefchyk, S. J., Jell, R. M. & Jordan, L. M. Reversible cooling of the brainstem reveals areas required for mesencephalic locomotor region evoked treadmill locomotion. Exp. Brain Res. 56, 257–262 (1984).

    CAS  PubMed  Google Scholar 

  11. Steeves, J. D. & Jordan, L. M. Localization of a descending pathway in the spinal cord which is necessary for controlled treadmill locomotion. Neurosci. Lett. 20, 283–288 (1980).

    CAS  PubMed  Google Scholar 

  12. Bouvier, J. et al. Descending command neurons in the brainstem that halt locomotion. Cell 163, 1191–1203 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Gordon, I. T. & Whelan, P. J. Brainstem modulation of locomotion in the neonatal mouse spinal cord. J. Physiol. 586, 2487–2497 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Favorov, O. V., Nilaweera, W. U., Miasnikov, A. A. & Beloozerova, I. N. Activity of somatosensory-responsive neurons in high subdivisions of SI cortex during locomotion. J. Neurosci. 35, 7763–7776 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Fitzsimmons, N. A., Lebedev, M. A., Peikon, I. D. & Nicolelis, M. A. Extracting kinematic parameters for monkey bipedal walking from cortical neuronal ensemble activity. Front. Integr. Neurosci. 3, 3 (2009).

    PubMed  PubMed Central  Google Scholar 

  16. Chapin, J. K. & Woodward, D. J. Somatic sensory transmission to the cortex during movement: gating of single cell responses to touch. Exp. Neurol. 78, 654–669 (1982).

    CAS  PubMed  Google Scholar 

  17. Chapin, J. K. & Woodward, D. J. Somatic sensory transmission to the cortex during movement: phasic modulation over the locomotor step cycle. Exp. Neurol. 78, 670–684 (1982).

    CAS  PubMed  Google Scholar 

  18. London, B. M. & Miller, L. E. Responses of somatosensory area 2 neurons to actively and passively generated limb movements. J. Neurophysiol. 109, 1505–1513 (2013).

    CAS  PubMed  Google Scholar 

  19. Matyas, F. et al. Motor control by sensory cortex. Science 330, 1240–1243 (2010).

    CAS  PubMed  Google Scholar 

  20. Auffret, M. et al. Optogenetic stimulation of cortex to map evoked whisker movements in awake head-restrained mice. Neuroscience 368, 199–213 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Sessle, B. J. & Wiesendanger, M. Structural and functional definition of the motor cortex in the monkey (Macaca fascicularis). J. Physiol. 323, 245–265 (1982).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Wilder Penfield, E. B. Somatic motor and sensory representation in the cerebral cortex of man as studied by electrical stimulation. Brain 60, 389–443 (1937).

    Google Scholar 

  23. Blaszczyk, J. W. & Dobrzecka, C. Effects of unilateral somatosensory cortex lesion upon locomotion in dogs. Acta Neurobiol. Exp. (Wars.) 55, 133–140 (1995).

    CAS  Google Scholar 

  24. Richardson, A. G. et al. The effects of acute cortical somatosensory deafferentation on grip force control. Cortex 74, 1–8 (2016).

    PubMed  Google Scholar 

  25. Clark, F. M. & Proudfit, H. K. The projection of locus coeruleus neurons to the spinal cord in the rat determined by anterograde tracing combined with immunocytochemistry. Brain Res. 538, 231–245 (1991).

    CAS  PubMed  Google Scholar 

  26. Wise, S. P. & Jones, E. G. Cells of origin and terminal distribution of descending projections of the rat somatic sensory cortex. J. Comp. Neurol. 175, 129–157 (1977).

    CAS  PubMed  Google Scholar 

  27. Ueno, M. et al. Corticospinal circuits from the sensory and motor cortices differentially regulate skilled movements through distinct spinal interneurons. Cell Rep. 23, 1286–1300 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Cowley, K. C. & Schmidt, B. J. Regional distribution of the locomotor pattern-generating network in the neonatal rat spinal cord. J. Neurophysiol. 77, 247–259 (1997).

    CAS  PubMed  Google Scholar 

  29. Alexander, G. M. et al. Remote control of neuronal activity in transgenic mice expressing evolved G protein-coupled receptors. Neuron 63, 27–39 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Armbruster, B. N., Li, X., Pausch, M. H., Herlitze, S. & Roth, B. L. Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand. Proc. Natl Acad. Sci. USA 104, 5163–5168 (2007).

    PubMed  Google Scholar 

  31. Magnus, C. J. et al. Chemical and genetic engineering of selective ion channel–ligand interactions. Science 333, 1292–1296 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Bellardita, C. & Kiehn, O. Phenotypic characterization of speed-associated gait changes in mice reveals modular organization of locomotor networks. Curr. Biol. 25, 1426–1436 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Keriel, A., Rene, C., Galer, C., Zabner, J. & Kremer, E. J. Canine adenovirus vectors for lung-directed gene transfer: efficacy, immune response and duration of transgene expression using helper-dependent vectors. J. Virol. 80, 1487–1496 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Schwarz, L. A. et al. Viral-genetic tracing of the input–output organization of a central noradrenaline circuit. Nature 524, 88–92 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Goulding, M. Circuits controlling vertebrate locomotion: moving in a new direction. Nat. Rev. Neurosci. 10, 507–518 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Grillner, S. & Jessell, T. M. Measured motion: searching for simplicity in spinal locomotor networks. Curr. Opin. Neurobiol. 19, 572–586 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. McLean, D. L. & Dougherty, K. J. Peeling back the layers of locomotor control in the spinal cord. Curr. Opin. Neurobiol. 33, 63–70 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Wise, S. P. The primate premotor cortex: past, present and preparatory. Annu. Rev. Neurosci. 8, 1–19 (1985).

    CAS  PubMed  Google Scholar 

  39. Petersen, C. C. Cortical control of whisker movement. Annu. Rev. Neurosci. 37, 183–203 (2014).

    CAS  PubMed  Google Scholar 

  40. Semba, K. & Komisaruk, B. R. Neural substrates of two different rhythmical vibrissal movements in the rat. Neuroscience 12, 761–774 (1984).

    CAS  PubMed  Google Scholar 

  41. Crochet, S. & Petersen, C. C. Correlating whisker behavior with membrane potential in barrel cortex of awake mice. Nat. Neurosci. 9, 608–610 (2006).

    CAS  PubMed  Google Scholar 

  42. Niell, C. M. & Stryker, M. P. Modulation of visual responses by behavioral state in mouse visual cortex. Neuron 65, 472–479 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Keller, G. B., Bonhoeffer, T. & Hubener, M. Sensorimotor mismatch signals in primary visual cortex of the behaving mouse. Neuron 74, 809–815 (2012).

    CAS  PubMed  Google Scholar 

  44. Ruder, L., Takeoka, A. & Arber, S. Long-distance descending spinal neurons ensure quadrupedal locomotor stability. Neuron 92, 1063–1078 (2016).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This research was supported by CIHR Grant MOP13683 (M.G.F.), CIHR Grant MOP 86470 (S.G.), an AOSPINE Young Investigator Research Grant (K.S.), the Halbert Chair in Neural Repair and Regeneration (M.G.F.) and the DeZwirek Foundation (M.G.F.). S.K.K. was supported by the Onassis Foundation. We thank C. Castro and S. Sivakumaran for technical assistance and S. Arber for the FLExFRT-PSAML141F,Y115F-GlyR plasmid (Friedrich Miescher Institute).

Author information

Author notes

  1. Alex M. Laliberte

    Present address: Department of Biology, University of Ottawa, Ottawa, Ontario, Canada

  2. These authors contributed equally: Spyridon K. Karadimas, Kajana Satkunendrarajah.

Authors and Affiliations

  1. Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada

    Spyridon K. Karadimas & Michael G. Fehlings

  2. Krembil Research Institute, University Health Network, Toronto, Ontario, Canada

    Spyridon K. Karadimas, Kajana Satkunendrarajah, Alex M. Laliberte, Dene Ringuette, Iliya Weisspapir, Lijun Li & Michael G. Fehlings

  3. Department of Neurosurgery, Medical College of Wisconsin, Clement J. Zablocki VA Medical Center, Milwaukee, WI, USA

    Kajana Satkunendrarajah

  4. The Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada

    Dene Ringuette

  5. Department of Physiology, University of Alberta, Edmonton, Alberta, Canada

    Simon Gosgnach

Authors
  1. Spyridon K. Karadimas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kajana Satkunendrarajah
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alex M. Laliberte
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dene Ringuette
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Iliya Weisspapir
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lijun Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Simon Gosgnach
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Michael G. Fehlings
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

S.K.K., K.S. and M.G.F. designed all experiments. S.K.K. performed viral tracings, anatomical investigations, behavioral experiments and data analysis. K.S. performed viral tracings, anatomical investigations, behavioral experiments, all electrophysiological recordings and data analysis. A.M.L. performed the molecular and viral work, behavioral experiments, data analysis and statistics. L.L. provided technical assistance with the in vitro and in vivo lumbar field potential recordings. D.R. performed behavioral tracking and electrophysiology data analysis for the in vivo SI-cortical recording in freely moving mice. I.W. participated in the cortical electrode implantations. S.K.K., K.S., S.G., A.M.L. and M.G.F. wrote the paper, with contributions from D.R. M.G.F. supervised the work and provided the funding for the work.

Corresponding authors

Correspondence to Spyridon K. Karadimas, Kajana Satkunendrarajah or Michael G. Fehlings.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Extended data

Extended Data Fig. 1 Decorrelation analysis of animal velocity and somatosensory activity.

Decorrelation of animal velocity and somatosensory activity from panel Fig. 1(c) across artificially shifted temporal correspondence. The correlation plots in Fig. 1(d) correspond to relationship at the zero temporal shift. Positive shift time corresponds to velocity compared to latter somatosensory activity. (n = 8 mice).

Extended Data Fig. 2 Control SI stimulation in ChR2−/− mice does not increase locomotor frequency.

a, Representative ENG recordings of locomotor like activity from ipsilateral L2 and L5 ventral roots induced with 7 uM NMDA and 10 uM 5-HT. of a ChR2-/- mice (baseline). Optogenetic stimulation of the SI neurons in these mice did not evoke an increase in the frequency of locomotor-realted burst activity (SI stimulation) (bottom). b, Relative change in frequency of locomotor-like activity before optical stimulation of SI (red) and during SI optical stimulation (blue) in ChR2-/- mice. No significant difference was revealed between the two conditions (two-tailed paired t-test, p = 0.759). n = 3 mice. Group data are presented as mean ± s.e.m.

Source data

Extended Data Fig. 3 SI pyramidal neurons project to intermediate gray zone of cervical spinal cord.

a, AAVDJ-syn1-DIO-EGFP were injected unilaterally into Emx1::cre mice (n = 3). b, SI pyramidal neurons expressing GFP at the AAVDJ-syn1-DIO-EGFP injection site. c, Confocal images of 30 μm-thick transverse sections of the cervical spinal cord of the same animal contained eGFP+ projections in the intermediate gray matter of C4-7. d, Heat map reveal dense projections mainly in the intermediate gray zone.

Extended Data Fig. 4 Effect of SI stimulation on locomotion after KA washout.

Baseline ENG recordings of locomotor like activity from ipsilateral L2 and L5 ventral roots of a P0-3 Emx1::cre; Ai27D offspring one hour after KA perfusion in the cervical cord has been terminated (Top). Optogenetic stimulation of the SI neurons one hour after KA perfusion in the cervical cord has been terminated increases the frequency of locomotor-like bursting activity. (n = 4 mice) (Bottom).

Extended Data Fig. 5 Manipulation of the SI locomotor pathway does not change the general locomotor capability.

a, Bar graphs showing no change in the stride length after CNO administration. b, Bar graphs demonstrating the forepaw and hindpaw base of support before and after PSEM or CNO administration. c, Regularity index of mice before and after manipulation of the SI locomotor pathway. d, Circular diagrams showing that phase dispersions consistent with the trot gait pattern were preserved after silencing or activation of the SI locomotor pathway. e, Bar graphs demonstrate the lack of effects of the manipulation of the sensory locomotor pathway on the print width and print length of both forepaws and hindpaws. Data were extracted using Catwalk XT software (repeated measures one-way ANOVA with Dunnett’s multiple comparisons test,* indicates p < 0.05. n = 7 mice). Group data are presented as mean ± s.e.m.

Source data

Extended Data Fig. 6 Stimulation of the SI locomotor pathway does not induce neuropathic pain.

Bar graphs showing the intensity of signal obtained from forepaws and hindpaws during locomotion on the Catwalk gait analysis system do not change after CNO administration. Data were analyzed using two-tailed paired t-tests (n = 7 mice). No statistically significant differences were observed (Related to Fig. 3). Group data are presented as mean ± s.e.m.

Source data

Extended Data Fig. 7 Stimulation of the SI locomotor pathway does not change the reaction to noxious stimuli.

a, Bar graphs showing the frequency of forepaw and hindpaw withdrawal resulting from 10 non-consecutive touches on each paw with the 0.4 g von Frey monofilament during both baseline and CNO conditions. b, Bar graph showing the latency to withdrawal of the tail following exposure to mild thermal stimulus in both baseline and CNO conditions, with each data point representing the average of three trials. Data were analyzed by two-tailed paired t-test (n = 7 mice). No statistically significant differences were observed. Group data are presented as mean ± s.e.m.

Source data

Extended Data Fig. 8 Inactivation of the SI neurons projecting to cervical cord does not decrease the forelimb strength.

Bar graph showing mean grip strength for mice before and after PSEM injection to inhibit SI neurons. Data were analyzed by two-tailed paired t-test (n = 7 mice). No statistically significant differences were observed. Group data are presented as mean ± s.e.m.

Source data

Extended Data Fig. 9 Anatomical distribution of the cervical excitatory cells projecting to ventromedial region of upper lumbar spinal cord.

a, Vglut2::cre mice were crossed with an Ai65(RCFL-tdT) line that contains FRT-stop-FRT and LoxP-stop-LoxP double cassettes ahead of tdTomato. Laminae VII/VIII/X of L1 spinal segments of adult Vglut2::cre;Ai65(RCFL-tdT) were unilaterally injected with the retrograde virus CAV2-FLExloxP –Flp (n = 2 mice). b, Laminar distribution of the tdTomato-positive lumbar-projecting cervical glutamatergic cells. c, Density plot demonstrating the distribution of the lumbar projecting glutamatergic cells in the cervical enlargement. Group data are presented as mean ± s.e.m.

Supplementary information

Supplementary Information

Supplementary Tables 1 and 2.

Reporting Summary

Supplementary Video 1

Simultaneous motion tracking and SI electrophysiological recording in freely behaving animals. Animal position (indicated by white dot superimposed on mouse) was extracted from the video and used for concurrent velocity calculation.

Supplementary Data

Supplementary data corresponding to Fig. 1. SI activity and velocity values with corresponding time stamps.

Source data

Source Data Fig. 2

Statistical Source Data.

Source Data Fig. 4

Statistical Source Data.

Source Data Fig. 5

Statistical Source Data.

Source Data Fig. 6

Statistical Source Data.

Source Data Fig. 7

Statistical Source Data.

Source Data Extended Data Fig. 2

Statistical Source Data.

Source Data Extended Data Fig. 5

Statistical Source Data.

Source Data Extended Data Fig. 6

Statistical Source Data.

Source Data Extended Data Fig. 7

Statistical Source Data.

Source Data Extended Data Fig. 8

Statistical Source Data.

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Karadimas, S.K., Satkunendrarajah, K., Laliberte, A.M. et al. Sensory cortical control of movement. Nat Neurosci 23, 75–84 (2020). https://doi.org/10.1038/s41593-019-0536-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41593-019-0536-7

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing