Shared Cortex-Cerebellum Dynamics in the Execution and Learning of a Motor Task

Throughout mammalian neocortex, layer 5 pyramidal (L5) cells project via the pons to a vast number of cerebellar granule cells (GrCs), forming a fundamental pathway. Yet, it is unknown how neuronal dynamics are transformed through the L5→GrC pathway. Here, by directly comparing premotor L5 and GrC activity during a forelimb movement task using dual-site two-photon Ca2+ imaging, we found that in expert mice, L5 and GrC dynamics were highly similar. L5 cells and GrCs shared a common set of task-encoding activity patterns, possessed similar diversity of responses, and exhibited high correlations comparable to local correlations among L5 cells. Chronic imaging revealed that these dynamics co-emerged in cortex and cerebellum over learning: as behavioral performance improved, initially dissimilar L5 cells and GrCs converged onto a shared, low-dimensional, task-encoding set of neural activity patterns. Thus, a key function of cortico-cerebellar communication is the propagation of shared dynamics that emerge during learning.

[1]  H. Sompolinsky,et al.  Transition to chaos in random neuronal networks , 2015, 1508.06486.

[2]  Zhanmin Lin,et al.  Excitatory Cerebellar Nucleocortical Circuit Provides Internal Amplification during Associative Conditioning , 2016, Neuron.

[3]  Ben Deverett,et al.  Cerebellar granule cells acquire a widespread predictive feedback signal during motor learning , 2017, Nature Neuroscience.

[4]  Zengcai V. Guo,et al.  A motor cortex circuit for motor planning and movement , 2015, Nature.

[5]  Thomas D. Mrsic-Flogel,et al.  Cerebellar contribution to preparatory activity in motor neocortex , 2018 .

[6]  D. Marr A theory of cerebellar cortex , 1969, The Journal of physiology.

[7]  E. Pnevmatikakis,et al.  NoRMCorre: An online algorithm for piecewise rigid motion correction of calcium imaging data , 2017, Journal of Neuroscience Methods.

[8]  Mark J. Schnitzer Visualizing mammalian brain area interactions by dual-axis two-photon calcium imaging , 2015, CLEO 2015.

[9]  Sandro Romani,et al.  Low-Dimensional and Monotonic Preparatory Activity in Mouse Anterior Lateral Motor Cortex , 2018, The Journal of Neuroscience.

[10]  M. Sahani,et al.  Cortical control of arm movements: a dynamical systems perspective. , 2013, Annual review of neuroscience.

[11]  J G Bjaalie,et al.  Salient anatomic features of the cortico-ponto-cerebellar pathway. , 1997, Progress in brain research.

[12]  M. Fujita,et al.  Adaptive filter model of the cerebellum , 1982, Biological Cybernetics.

[13]  Claudia Clopath,et al.  Sparse synaptic connectivity is required for decorrelation and pattern separation in feedforward networks , 2017, Nature Communications.

[14]  Haim Sompolinsky,et al.  Optimal Degrees of Synaptic Connectivity , 2017, Neuron.

[15]  K. Kissa,et al.  Preferential transduction of neurons by canine adenovirus vectors and their efficient retrograde transport in vivo , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[16]  Liqun Luo,et al.  Viral-genetic tracing of the input–output organization of a central norepinephrine circuit , 2015, Nature.

[17]  E. Miller,et al.  Gradual progression from sensory to task-related processing in cerebral cortex , 2017, Proceedings of the National Academy of Sciences.

[18]  Zhenyu Gao,et al.  Distributed synergistic plasticity and cerebellar learning , 2012, Nature Reviews Neuroscience.

[19]  S. Nelson,et al.  A Resource of Cre Driver Lines for Genetic Targeting of GABAergic Neurons in Cerebral Cortex , 2011, Neuron.

[20]  Sophie Denève,et al.  The Brain as an Efficient and Robust Adaptive Learner , 2017, Neuron.

[21]  Michael N. Economo,et al.  A cortico-cerebellar loop for motor planning , 2018, Nature.

[22]  Jonathan Kadmon,et al.  Optimal Architectures in a Solvable Model of Deep Networks , 2016, NIPS.

[23]  J. Albus A Theory of Cerebellar Function , 1971 .

[24]  Allan R. Jones,et al.  A toolbox of Cre-dependent optogenetic transgenic mice for light-induced activation and silencing , 2012, Nature Neuroscience.

[25]  Surya Ganguli,et al.  On simplicity and complexity in the brave new world of large-scale neuroscience , 2015, Current Opinion in Neurobiology.

[26]  M. Häusser,et al.  High-fidelity transmission of sensory information by single cerebellar mossy fibre boutons , 2007, Nature.

[27]  P. Strick,et al.  Cerebellar Loops with Motor Cortex and Prefrontal Cortex of a Nonhuman Primate , 2003, The Journal of Neuroscience.

[28]  L. Luo,et al.  Cerebellar granule cells encode the expectation of reward , 2017, Nature.

[29]  Charles Watson,et al.  Distribution of neurons in functional areas of the mouse cerebral cortex reveals quantitatively different cortical zones , 2013, Front. Neuroanat..

[30]  D. Wolpert,et al.  Motor Planning, Not Execution, Separates Motor Memories , 2016, Neuron.

[31]  Hinrich Schütze,et al.  Introduction to information retrieval , 2008 .

[32]  J. Kleim,et al.  The organization of the forelimb representation of the C57BL/6 mouse motor cortex as defined by intracortical microstimulation and cytoarchitecture. , 2011, Cerebral cortex.

[33]  M. Häusser,et al.  Integration of quanta in cerebellar granule cells during sensory processing , 2004, Nature.

[34]  C. Gerfen,et al.  GENSAT BAC Cre-Recombinase Driver Lines to Study the Functional Organization of Cerebral Cortical and Basal Ganglia Circuits , 2013, Neuron.

[35]  H. Sompolinsky,et al.  Sparseness and Expansion in Sensory Representations , 2014, Neuron.

[36]  Adam Possner,et al.  Cerebellum , 2012, Neurology.

[37]  David Pfau,et al.  Simultaneous Denoising, Deconvolution, and Demixing of Calcium Imaging Data , 2016, Neuron.

[38]  M. Cohen,et al.  Measuring and interpreting neuronal correlations , 2011, Nature Neuroscience.

[39]  Suzana Herculano-Houzel,et al.  Coordinated Scaling of Cortical and Cerebellar Numbers of Neurons , 2010, Front. Neuroanat..

[40]  Adam Santoro,et al.  Structural foundations of optogenetics: Determinants of channelrhodopsin ion selectivity , 2015, Proceedings of the National Academy of Sciences.

[41]  T. Ruigrok,et al.  Organization of Cerebral Projections to Identified Cerebellar Zones in the Posterior Cerebellum of the Rat , 2012, The Journal of Neuroscience.

[42]  Simon X. Chen,et al.  Emergence of reproducible spatiotemporal activity during motor learning , 2014, Nature.

[43]  Nathan C. Klapoetke,et al.  Transgenic Mice for Intersectional Targeting of Neural Sensors and Effectors with High Specificity and Performance , 2015, Neuron.

[44]  Michael Häusser,et al.  Multimodal sensory integration in single cerebellar granule cells in vivo , 2015, eLife.

[45]  Benjamin F. Grewe,et al.  Visualizing mammalian brain area interactions by dual-axis two-photon calcium imaging , 2015, 2015 Conference on Lasers and Electro-Optics (CLEO).

[46]  R. Angus Silver,et al.  Network Structure within the Cerebellar Input Layer Enables Lossless Sparse Encoding , 2014, Neuron.

[47]  Martin T. Wiechert,et al.  Synaptic diversity enables temporal coding of coincident multi-sensory inputs in single neurons , 2015, Nature Neuroscience.

[48]  Egidio D'Angelo,et al.  Silencing the majority of cerebellar granule cells uncovers their essential role in motor learning and consolidation. , 2013, Cell reports.

[49]  Abigail L Person,et al.  Morphological Constraints on Cerebellar Granule Cell Combinatorial Diversity , 2017, The Journal of Neuroscience.

[50]  R. Barton,et al.  Rapid evolution of the cerebellum in humans and other great apes. , 2014, Current biology : CB.

[51]  Stefan R. Pulver,et al.  Ultra-sensitive fluorescent proteins for imaging neuronal activity , 2013, Nature.

[52]  Torgeir Moberget,et al.  Annals of the New York Academy of Sciences Cerebellar Contributions to Motor Control and Language Comprehension: Searching for Common Computational Principles , 2022 .

[53]  Cathrin B. Canto,et al.  Role of Synchronous Activation of Cerebellar Purkinje Cell Ensembles in Multi-joint Movement Control , 2015, Current Biology.

[54]  Ruben Portugues,et al.  Sensorimotor Representations in Cerebellar Granule Cells in Larval Zebrafish Are Dense, Spatially Organized, and Non-temporally Patterned , 2017, Current Biology.

[55]  Adam W Hantman,et al.  Convergence of pontine and proprioceptive streams onto multimodal cerebellar granule cells , 2013, eLife.