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Cerebellum involvement in cortical sensorimotor circuits for the control of voluntary movements

Nature Neuroscience volume 17, pages 1233–1239 (2014)Cite this article

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Abstract

Sensorimotor integration is crucial to perception and motor control. How and where this process takes place in the brain is still largely unknown. Here we analyze the cerebellar contribution to sensorimotor integration in the whisker system of mice. We identify an area in the cerebellum where cortical sensory and motor inputs converge at the cellular level. Optogenetic stimulation of this area affects thalamic and motor cortex activity, alters parameters of ongoing movements and thereby modifies qualitatively and quantitatively touch events against surrounding objects. These results shed light on the cerebellum as an active component of sensorimotor circuits and show the importance of sensorimotor cortico-cerebellar loops in the fine control of voluntary movements.

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Figure 1: Autofluorescence imaging of sensory and motor cortical inputs in the cerebellum.
Figure 2: vM1 and vS1 inputs form separate pathways in the pontine nucleus and converge in the lateral part of crus I.
Figure 3: Sensory and motor cortical inputs to the cerebellum converge on single cells in the lateral cerebellum.
Figure 4: Inhibition-excitation sequence in the ascending cerebello-thalamo-cortical pathway following optogenetic activation of Purkinje cells.
Figure 5: Activation of the motor cortex after optogenetic stimulation of Purkinje cells in the lateral cerebellum of anesthetized mice.
Figure 6: Optogenetic stimulation of Purkinje cells in the lateral cerebellum modulates whisker movements monitored by high-speed videography in awake mice.
Figure 7: Effect of cerebellar stimulation on touch.

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References

  1. Kleinfeld, D. & Deschênes, M. Neuronal basis for object location in the vibrissa scanning sensorimotor system. Neuron 72, 455–468 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Grant, R.A., Mitchinson, B., Fox, C.W. & Prescott, T.J. Active touch sensing in the rat: anticipatory and regulatory control of whisker movements during surface exploration. J. Neurophysiol. 101, 862–874 (2009).

    PubMed  Google Scholar 

  3. Bosman, L.W.J. et al. Encoding of whisker input by cerebellar Purkinje cells. J. Physiol. (Lond.) 588, 3757–3783 (2010).

    CAS  Google Scholar 

  4. Morissette, J. & Bower, J.M. Contribution of somatosensory cortex to responses in the rat cerebellar granule cell layer following peripheral tactile stimulation. Exp. Brain Res. 109, 240–250 (1996).

    CAS  PubMed  Google Scholar 

  5. O'Connor, S.M., Berg, R.W. & Kleinfeld, D. Coherent electrical activity between vibrissa sensory areas of cerebellum and neocortex is enhanced during free whisking. J. Neurophysiol. 87, 2137–2148 (2002).

    PubMed  Google Scholar 

  6. Jenkinson, E.W. & Glickstein, M. Whiskers, barrels, and cortical efferent pathways in gap crossing by rats. J. Neurophysiol. 84, 1781–1789 (2000).

    CAS  PubMed  Google Scholar 

  7. Lang, E.J., Sugihara, I. & Llinás, R. Olivocerebellar modulation of motor cortex ability to generate vibrissal movements in rat. J. Physiol. (Lond.) 571, 101–120 (2006).

    CAS  Google Scholar 

  8. Reinert, K.C., Dunbar, R.L., Gao, W., Chen, G. & Ebner, T.J. Flavoprotein autofluorescence imaging of neuronal activation in the cerebellar cortex in vivo. J. Neurophysiol. 92, 199–211 (2004).

    CAS  PubMed  Google Scholar 

  9. Mao, T. et al. Long-range neuronal circuits underlying the interaction between sensory and motor cortex. Neuron 72, 111–123 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Ferezou, I. et al. Spatiotemporal dynamics of cortical sensorimotor integration in behaving mice. Neuron 56, 907–923 (2007).

    CAS  PubMed  Google Scholar 

  11. Schwarz, C. & Thier, P. Modular organization of the pontine nuclei: dendritic fields of identified pontine projection neurons in the rat respect the borders of cortical afferent fields. J. Neurosci. 15, 3475–3489 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Leergaard, T.B. et al. Three-dimensional topography of corticopontine projections from rat sensorimotor cortex: comparisons with corticostriatal projections reveal diverse integrative organization. J. Comp. Neurol. 478, 306–322 (2004).

    PubMed  Google Scholar 

  13. Apps, R. & Hawkes, R. Cerebellar cortical organization: a one-map hypothesis. Nat. Rev. Neurosci. 10, 670–681 (2009).

    CAS  PubMed  Google Scholar 

  14. Voogd, J. & Ruigrok, T.J.H. The organization of the corticonuclear and olivocerebellar climbing fiber projections to the rat cerebellar vermis: the congruence of projection zones and the zebrin pattern. J. Neurocytol. 33, 5–21 (2004).

    PubMed  Google Scholar 

  15. Odeh, F., Ackerley, R., Bjaalie, J.G. & Apps, R. Pontine maps linking somatosensory and cerebellar cortices are in register with climbing fiber somatotopy. J. Neurosci. 25, 5680–5690 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Sugihara, I. & Shinoda, Y. Molecular, topographic, and functional organization of the cerebellar nuclei: analysis by three-dimensional mapping of the olivonuclear projection and aldolase C labeling. J. Neurosci. 27, 9696–9710 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Van Dijck, G. et al. Probabilistic identification of cerebellar cortical neurones across species. PLoS ONE 8, e57669 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Suzuki, L., Coulon, P., Sabel-Goedknegt, E.H. & Ruigrok, T.J.H. Organization of cerebral projections to identified cerebellar zones in the posterior cerebellum of the rat. J. Neurosci. 32, 10854–10869 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Allen, G.I. & Tsukahara, N. Cerebrocerebellar communication systems. Physiol. Rev. 54, 957–1006 (1974).

    CAS  PubMed  Google Scholar 

  20. Andersson, G. Demonstration of a cuneate relay in a cortico-olivo-cerebellar pathway in the cat. Neurosci. Lett. 46, 47–52 (1984).

    CAS  PubMed  Google Scholar 

  21. Kelly, R.M. & Strick, P.L. Cerebellar loops with motor cortex and prefrontal cortex of a nonhuman primate. J. Neurosci. 23, 8432–8444 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Chaumont, J. et al. Clusters of cerebellar Purkinje cells control their afferent climbing fiber discharge. Proc. Natl. Acad. Sci. USA 110, 16223–16228 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Aumann, T.D., Ivanusic, J. & Horne, M.K. Arborisation and termination of single motor thalamocortical axons in the rat. J. Comp. Neurol. 396, 121–130 (1998).

    CAS  PubMed  Google Scholar 

  24. Haiss, F. & Schwarz, C. Spatial segregation of different modes of movement control in the whisker representation of rat primary motor cortex. J. Neurosci. 25, 1579–1587 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  26. Herculano-Houzel, S. Coordinated scaling of cortical and cerebellar numbers of neurons. Front. Neuroanat. 4, 12 (2010).

    PubMed  PubMed Central  Google Scholar 

  27. Leergaard, T.B. & Bjaalie, J. Topography of the complete corticopontine projection: From experiments to principal maps. Front. Neurosci. 1, 211–223 (2007).

    PubMed  PubMed Central  Google Scholar 

  28. Lu, X., Miyachi, S., Ito, Y., Nambu, A. & Takada, M. Topographic distribution of output neurons in cerebellar nuclei and cortex to somatotopic map of primary motor cortex. Eur. J. Neurosci. 25, 2374–2382 (2007).

    PubMed  Google Scholar 

  29. Alloway, K.D. Information processing streams in rodent barrel cortex: the differential functions of barrel and septal circuits. Cereb. Cortex 18, 979–989 (2008).

    PubMed  Google Scholar 

  30. Woolston, D.C., Kassel, J. & Gibson, J.M. Trigeminocerebellar mossy fiber branching to granule cell layer patches in the rat cerebellum. Brain Res. 209, 255–269 (1981).

    CAS  PubMed  Google Scholar 

  31. Holtzman, T., Cerminara, N.L., Edgley, S.A. & Apps, R. Characterization in vivo of bilaterally branching pontocerebellar mossy fibre to Golgi cell inputs in the rat cerebellum. Eur. J. Neurosci. 29, 328–339 (2009).

    PubMed  Google Scholar 

  32. Huang, C.-C. et al. Convergence of pontine and proprioceptive streams onto multimodal cerebellar granule cells. Elife 2, e00400 (2013).

    PubMed  PubMed Central  Google Scholar 

  33. Futami, T., Kano, M., Sento, S. & Shinoda, Y. Synaptic organization of the cerebello-thalamo-cerebral pathway in the cat. III. Cerebellar input to corticofugal neurons destined for different subcortical nuclei in areas 4 and 6. Neurosci. Res. 3, 321–344 (1986).

    CAS  PubMed  Google Scholar 

  34. Na, J., Kakei, S. & Shinoda, Y. Cerebellar input to corticothalamic neurons in layers V and VI in the motor cortex. Neurosci. Res. 28, 77–91 (1997).

    CAS  PubMed  Google Scholar 

  35. Teune, T.M., van der Burg, J., van der Moer, J., Voogd, J. & Ruigrok, T.J.H. Topography of cerebellar nuclear projections to the brain stem in the rat. Prog. Brain Res. 124, 141–172 (2000).

    CAS  PubMed  Google Scholar 

  36. Jörntell, H. & Ekerot, C.F. Topographical organization of projections to cat motor cortex from nucleus interpositus anterior and forelimb skin. J. Physiol. 514 (pt. 2): 551–566 (1999).

    PubMed  PubMed Central  Google Scholar 

  37. Sasaki, K., Kawaguchi, S., Oka, H., Sakai, M. & Mizuno, N. Electrophysiological studies on the cerebellocerebral projections in monkeys. Exp. Brain Res. 24, 495–507 (1976).

    CAS  PubMed  Google Scholar 

  38. Holdefer, R.N., Miller, L.E., Chen, L.L. & Houk, J.C. Functional connectivity between cerebellum and primary motor cortex in the awake monkey. J. Neurophysiol. 84, 585–590 (2000).

    CAS  PubMed  Google Scholar 

  39. Rowland, N.C., Goldberg, J.A. & Jaeger, D. Cortico-cerebellar coherence and causal connectivity during slow-wave activity. Neuroscience 166, 698–711 (2010).

    CAS  PubMed  Google Scholar 

  40. Parsons, L.M. et al. Lateral cerebellar hemispheres actively support sensory acquisition and discrimination rather than motor control. Learn. Mem. 4, 49–62 (1997).

    CAS  PubMed  Google Scholar 

  41. Gao, J.H. et al. Cerebellum implicated in sensory acquisition and discrimination rather than motor control. Science 272, 545–547 (1996).

    CAS  PubMed  Google Scholar 

  42. Knutsen, P.M. & Ahissar, E. Orthogonal coding of object location. Trends Neurosci. 32, 101–109 (2009).

    CAS  PubMed  Google Scholar 

  43. Boubenec, Y., Shulz, D.E. & Debrégeas, G. Whisker encoding of mechanical events during active tactile exploration. Front. Behav. Neurosci. 6, 74 (2012).

    PubMed  PubMed Central  Google Scholar 

  44. Sultan, F. et al. Unravelling cerebellar pathways with high temporal precision targeting motor and extensive sensory and parietal networks. Nat. Commun. 3, 924 (2012).

    PubMed  Google Scholar 

  45. Ito, M. Control of mental activities by internal models in the cerebellum. Nat. Rev. Neurosci. 9, 304–313 (2008).

    CAS  PubMed  Google Scholar 

  46. Liu, X., Robertson, E. & Miall, R.C. Neuronal activity related to the visual representation of arm movements in the lateral cerebellar cortex. J. Neurophysiol. 89, 1223–1237 (2003).

    PubMed  Google Scholar 

  47. Cerminara, N.L. An internal model of a moving visual target in the lateral cerebellum. J. Physiol. (Lond.) 587, 429–442 (2009).

    CAS  Google Scholar 

  48. Anderson, S.R. et al. An internal model architecture for novelty detection: implications for cerebellar and collicular roles in sensory processing. PLoS ONE 7, e44560 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Wolpert, D.M., Miall, R. & Kawato, M. Internal models in the cerebellum. Trends Cogn. Sci. 2, 338–347 (1998).

    CAS  PubMed  Google Scholar 

  50. Popa, D. et al. Functional role of the cerebellum in gamma-band synchronization of the sensory and motor cortices. J. Neurosci. 33, 6552–6556 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Shibuki, K. et al. Dynamic imaging of somatosensory cortical activity in the rat visualized by flavoprotein autofluorescence. J. Physiol. (Lond.) 549, 919–927 (2003).

    CAS  Google Scholar 

  52. Gao, H., de Solages, C. & Lena, C. Tetrode recordings in the cerebellar cortex. J. Physiol. Paris 106, 128–136 (2012).

    PubMed  Google Scholar 

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Acknowledgements

This work was supported by France's Agence Nationale de la Recherche (ANR-09-MNPS-38, ANR-11-BSV4-028 01, ANR-12-BSV4-0027), France's Centre National de la Recherche Scientifique (CNRS), France's Institut National de la Santé et de la Recherche Médicale (INSERM; C.L., D.P.), the Ecole Normale Supérieure (ENS), the Fondation pour la recherche médicale (FRM - FDT20120925324, R.D.P.), Labex Memolife (R.D.P.) and the European Union (CBTOUCH-FP7-People-2011-IEF, M.S.). We are grateful to B. Barbour, V. Ego-Stengel, D. Shulz, L. Bourdieu and J.-F. Léger for careful reading of the manuscript. We thank G. Parésys, Y. Cabirou and B. Mathieu for excellent technical assistance and A. Boudet for help with the autofluorescence video acquisition. This work received support under the program «Investissements d'Avenir» launched by the French Government and implemented by the ANR: ANR-10-LABX-54 MEMO LIFE, ANR-10-LABX-0087 IEC, ANR-11-IDEX-0001-02 PSL* Research University.

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Author notes

  1. Rémi D Proville and Maria Spolidoro: These authors contributed equally to this work.

  2. Daniela Popa and Clément Léna: These authors jointly direct this work.

Authors and Affiliations

  1. Institut de Biologie de l'Ecole Normale Supérieure, Paris, France

    Rémi D Proville, Maria Spolidoro, Nicolas Guyon, Guillaume P Dugué, Daniela Popa & Clément Léna

  2. Centre National de la Recherche Scientifique (CNRS) UMR8197, Paris, France

    Rémi D Proville, Maria Spolidoro, Nicolas Guyon, Guillaume P Dugué, Daniela Popa & Clément Léna

  3. Institut National de la Santé et de la Recherche Médicale (INSERM) U1024, Paris, France

    Rémi D Proville, Maria Spolidoro, Nicolas Guyon, Guillaume P Dugué, Daniela Popa & Clément Léna

  4. Center for Interdisciplinary Research in Biology, Collège de France, Paris, France

    Fekrije Selimi

  5. CNRS UMR7241, Paris, France

    Fekrije Selimi

  6. INSERM U1050, Paris, France

    Fekrije Selimi

  7. Institut des Neurosciences Cellulaires et Intégratives, CNRS UPR 3212, Université de Strasbourg, Strasbourg, France

    Philippe Isope

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Contributions

R.D.P., M.S., D.P. and C.L. designed the experiments and analyzed the data. R.D.P., M.S. and N.G. performed the experiments. G.P.D. helped with optogenetics development and performed pilot experiments. P.I. and F.S. provided access to unpublished tools. R.D.P., M.S. and C.L. wrote the manuscript.

Corresponding authors

Correspondence to Daniela Popa or Clément Léna.

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Integrated supplementary information

Supplementary Figure 1 Autofluorescence imaging of sensory and motor cortical inputs in the cerebellum in awake animals

Schematic representation and localization of the stimulation and imaging areas with examples of autofluorescence evoked on the cerebellar surface by stimulation of vM1 or vS1 and examples of response time courses after cortical stimulation (200-500 µA, 200 µs, 6 Hz for 3 s with 7 s pause; n=20 trials). Scale bar: 500 μm.

Supplementary Figure 2 Retrograde labeling of olivary inputs to lateral or medial crus I.

(a): Injections of red and green retrobeads respectively in medial and lateral Crus I produced labeling in two separate sets of pontine nucleus cells. (b): Injections of red retrobeads in medial Crus I produced labeling in the medial accessory olive (MAO) and dorsal accessory olive (DAO). (c). Injections of green retrobeads in lateral Crus I produced labeling in the most ventral part of the principal olive (PO) nucleus.

Supplementary Figure 3 Spike sorting in stimulation experiments.

(a) Example of raw unfiltered tetrode recordings in the cerebellum after stimulation of vM1. Each trace represents a single tetrode channel. (b) Examples of the same traces after high-pass filtering at 1kHz. Colored vertical bars represent sorted spikes from different cells. (c-d) the spikes isolated during the response period are similar to the spikes in baseline: (c) Example of 3 cells hand-clustered by polygon-cutting in 2-dimensional projections of the parameter space using Xclust (Matt Wilson, MIT). Spikes between stimulations and spikes in the 20 ms following the stimulation are represented with different color/symbol size and they exhibit the same amplitudes on the tetrode channels, and (d) their average unfiltered waveforms recorded from the four tetrode channels are also similar between stimulations in the 20 ms following the stimulations.

Supplementary Figure 4 Golgi cell responses to vS1, vM1.

Latencies of Golgi cell (GC) and Purkinje cell (PC) responses in lateral and medial Crus I; * = p < 0.05.

Supplementary Figure 5 Number of recorded cells.

Number of cells recorded with different stimulations. Note that cells recorded with stimulations of both vM1 and vS1 (M1&S1) are a subset of cells recorded during stimulation of either vM1 or vS1.

Supplementary Figure 6 Activation of the motor cortex after optogenetic stimulation of Purkinje cells in the lateral cerebellum of awake mice.

(a) Schematic representation of ascending cerebello-cortical pathway. (b) Examples of field potentials recorded in vM1 after stimulation of Crus I or Crus II on the cerebellum (green and blue dots respectively).

Supplementary Figure 7 Whisking parameters before and during optogenetic stimulation.

Average speed, period and amplitude of whisking before (Baseline) and during (Stim) lateral stimulation of Crus I

Supplementary Figure 8 Schematic representation of the described cortico-cerebellar loop

Cortical inputs from vS1 and vM1 (blue and red respectively) form two separate pathways in the pontine nucleus. Sensorimotor projection from the pons converge on the same Golgi cell (green) and, via granule cells (deep blue), Purkinje cell (orange) in the cerebellar cortex. Output from the cerebellum contact neurons in the cerebellar nuclei (purple) which in turn project to the motor thalamus (grey). Projections from the motor thalamus to the motor cortex close the cortico-cerebellar loop. Perturbation of activity in this loop leads to modulation of whisking set-point.

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Proville, R., Spolidoro, M., Guyon, N. et al. Cerebellum involvement in cortical sensorimotor circuits for the control of voluntary movements. Nat Neurosci 17, 1233–1239 (2014). https://doi.org/10.1038/nn.3773

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