Information Processing in the Hemisphere of the Cerebellar Cortex for Control of 1 Wrist Movement 2 3

A region of cerebellar lobules V and VI makes strong loop connections with the primary motor (M1) and premotor (PM) cortical areas and is assumed to play essential roles in limb motor control. To examine its functional role, we compared the activities of its input, intermediate, and output elements, i.e., mossy fibers (MFs), Golgi cells (GoCs), and Purkinje cells (PCs), in three monkeys performing wrist movements in two different forearm postures. The results revealed distinct steps of information processing. First, MF activities displayed temporal and directional properties that were remarkably similar to those of M1/PM neurons, suggesting that MFs relay near copies of outputs from these motor areas. Second, all GoCs had a stereotyped pattern of activity independent of movement direction or forearm posture. Instead, GoC activity resembled an average of all MF activities. Therefore, inhibitory GoCs appear to provide a filtering function that passes only prominently modulated MF inputs to granule cells. Third, PCs displayed highly complex spatiotemporal patterns of activity, with coordinate frames distinct from those of MF inputs and directional tuning that changed abruptly before movement onset. The complexity of PC activities may reflect rapidly changing properties of the peripheral motor apparatus during movement. Overall, the cerebellar cortex appears to transform a representation of outputs from M1/PM into different movement representations in a posture-dependent manner and could work as part of a forward model that predicts the state of the peripheral motor apparatus.

[1]  John Porrill,et al.  The cerebellum as an adaptive filter: a general model? , 2010, Functional neurology.

[2]  Professor Dr. John C. Eccles,et al.  The Cerebellum as a Neuronal Machine , 1967, Springer Berlin Heidelberg.

[3]  H. C. Hulscher,et al.  Between in and out: linking morphology and physiology of cerebellar cortical interneurons. , 2005, Progress in brain research.

[4]  Masao Ito Cerebellar circuitry as a neuronal machine , 2006, Progress in Neurobiology.

[5]  Xiaofeng Lu,et al.  Topographic distribution of output neurons in cerebellar nuclei and cortex to somatotopic map of primary motor cortex , 2007, The European journal of neuroscience.

[6]  G. Somjen,et al.  Focal synaptic potentials due to discrete mossy-fibre arrival volleys in the cerebellar cortex , 1987, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[7]  T. Ebner,et al.  Cerebellar Purkinje Cell Simple Spike Discharge Encodes Movement Velocity in Primates during Visuomotor Arm Tracking , 1999, The Journal of Neuroscience.

[8]  Teresa G. Martins,et al.  An improved and cost-effective methodology for the reduction of autofluorescence in direct immunofluorescence studies on formalin-fixed paraffin-embedded tissues. , 2007, European journal of histochemistry : EJH.

[9]  D. Hoffman,et al.  Muscle and movement representations in the primary motor cortex. , 1999, Science.

[10]  Tahl Holtzman,et al.  Different responses of rat cerebellar Purkinje cells and Golgi cells evoked by widespread convergent sensory inputs , 2006, The Journal of physiology.

[11]  N. Fisher,et al.  A correlation coefficient for circular data , 1983 .

[12]  Michael I. Jordan,et al.  An internal model for sensorimotor integration. , 1995, Science.

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

[14]  Tatsuya Kimura,et al.  Cerebellar complex spikes encode both destinations and errors in arm movements , 1998, Nature.

[15]  W. T. Thach Discharge of Purkinje and cerebellar nuclear neurons during rapidly alternating arm movements in the monkey. , 1968, Journal of neurophysiology.

[16]  T. Ebner,et al.  Force field effects on cerebellar Purkinje cell discharge with implications for internal models , 2006, Nature Neuroscience.

[17]  Peter W Dicke,et al.  The Role of the Monkey Dorsal Pontine Nuclei in Goal-Directed Eye and Hand Movements , 2009, The Journal of Neuroscience.

[18]  F. Zajac Muscle and tendon: properties, models, scaling, and application to biomechanics and motor control. , 1989, Critical reviews in biomedical engineering.

[19]  Daniel M. Wolpert,et al.  Forward Models for Physiological Motor Control , 1996, Neural Networks.

[20]  Maurice A. Smith,et al.  Motor Memory Is Encoded as a Gain-Field Combination of Intrinsic and Extrinsic Action Representations , 2012, Journal of Neuroscience.

[21]  P. Brodal,et al.  The cortical projection to the nucleus reticularis tegmenti pontis in the rhesus monkey , 2004, Experimental Brain Research.

[22]  A. M. Smith,et al.  Purkinje cell simple spike activity during grasping and lifting objects of different textures and weights. , 1990, Journal of neurophysiology.

[23]  J C Houk,et al.  Identification of unitary potentials in turtle cerebellum and correlations with structures in granular layer. , 1974, Journal of neurophysiology.

[24]  J. Houk,et al.  Movement-related inputs to intermediate cerebellum of the monkey. , 1993, Journal of neurophysiology.

[25]  N. Mano,et al.  Simple-spike activity of cerebellar Purkinje cells related to visually guided wrist tracking movement in the monkey. , 1980, Journal of neurophysiology.

[26]  Stefan Schaal,et al.  Forward models in visuomotor control. , 2002, Journal of neurophysiology.

[27]  P. Thier,et al.  Pontine reference frames for the sensory guidance of movement. , 2012, Cerebral cortex.

[28]  A B Vallbo,et al.  Directional tuning of human forearm muscle afferents during voluntary wrist movements , 2001, The Journal of physiology.

[29]  E De Schutter,et al.  Cerebellar Golgi cells in the rat: receptive fields and timing of responses to facial stimulation , 1999, The European journal of neuroscience.

[30]  Anthony R. Dickinson,et al.  Limb-Specific Representation for Reaching in the Posterior Parietal Cortex , 2008, The Journal of Neuroscience.

[31]  D. Pandya,et al.  Motor projections to the basis pontis in rhesus monkey , 2004, The Journal of comparative neurology.

[32]  D. Hoffman,et al.  Step-tracking movements of the wrist. IV. Muscle activity associated with movements in different directions. , 1999, Journal of neurophysiology.

[33]  Donna S. Hoffman,et al.  Releasing Dentate Nucleus Cells from Purkinje Cell Inhibition Generates Output from the Cerebrocerebellum , 2014, PloS one.

[34]  S. Delp,et al.  Variation of muscle moment arms with elbow and forearm position. , 1995, Journal of biomechanics.

[35]  Laurentiu S. Popa,et al.  Predictive and Feedback Performance Errors Are Signaled in the Simple Spike Discharge of Individual Purkinje Cells , 2012, The Journal of Neuroscience.

[36]  Timothy J. Ebner,et al.  Cerebellum Predicts the Future Motor State , 2008, The Cerebellum.

[37]  T. Ebner,et al.  Purkinje cell complex and simple spike changes during a voluntary arm movement learning task in the monkey. , 1992, Journal of neurophysiology.

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

[39]  Henrik Jörntell,et al.  Reciprocal Bidirectional Plasticity of Parallel Fiber Receptive Fields in Cerebellar Purkinje Cells and Their Afferent Interneurons , 2002, Neuron.

[40]  D. Hoffman,et al.  Direction of action is represented in the ventral premotor cortex , 2001, Nature Neuroscience.

[41]  J C Houk,et al.  Synaptic Transmission at Single Glomeruli in the Turtle Cerebellum , 1972, Science.

[42]  Masahiko Fujita,et al.  New Supervised Learning Theory Applied to Cerebellar Modeling for Suppression of Variability of Saccade End Points , 2013, Neural Computation.

[43]  P. Brodal,et al.  The projection from the nucleus reticularis tegmenti pontis to the cerebellum in the rhesus monkey , 2004, Experimental Brain Research.

[44]  P. Brodal,et al.  Further observations on the cerebellar projections from the pontine nuclei and the nucleus reticularis tegmenti pontis in the rhesus monkey , 1982, The Journal of comparative neurology.

[45]  M. Glickstein,et al.  Mossy-fibre sensory input to the cerebellum. , 1997, Progress in brain research.

[46]  M. Kawato,et al.  Encoding of movement dynamics by Purkinje cell simple spike activity during fast arm movements under resistive and assistive force fields. , 2007, Journal of neurophysiology.

[47]  N. Barmack,et al.  Functions of Interneurons in Mouse Cerebellum , 2008, The Journal of Neuroscience.

[48]  A. M. Smith,et al.  Cerebellar cortical activity during stretch of antagonist muscles. , 1986, Canadian journal of physiology and pharmacology.

[49]  D. Hoffman,et al.  Mossy fibers in the cerebellar hemisphere show delay activity in a delayed response task , 2014, Neuroscience Research.

[50]  Timothy J Ebner,et al.  Representation of limb kinematics in Purkinje cell simple spike discharge is conserved across multiple tasks. , 2011, Journal of neurophysiology.

[51]  M Glickstein,et al.  Tectopontine pathway in the cat: laminar distribution of cells of origin and visual properties of target cells in dorsolateral pontine nucleus. , 1979, Journal of neurophysiology.

[52]  L. Roncali,et al.  Non-traditional large neurons in the granular layer of the cerebellar cortex. , 2007, European journal of histochemistry : EJH.

[53]  J. Houk,et al.  Output organization of intermediate cerebellum of the monkey. , 1993, Journal of neurophysiology.

[54]  J. Kalaska,et al.  Differential relation of discharge in primary motor cortex and premotor cortex to movements versus actively maintained postures during a reaching task , 1996, Experimental Brain Research.

[55]  A P Georgopoulos,et al.  On the relations between the direction of two-dimensional arm movements and cell discharge in primate motor cortex , 1982, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[56]  J. Fritschy,et al.  Heterogeneity of glycinergic and gabaergic interneurons in the granule cell layer of mouse cerebellum , 2007, The Journal of comparative neurology.

[57]  R. Llinás,et al.  The mossy fibre-granule cell relay of the cerebellum and its inhibitory control by Golgi cells , 2004, Experimental Brain Research.

[58]  D E Hillman,et al.  The primate cerebellar cortex: a Golgi and electron microscopic study. , 1967, Progress in brain research.

[59]  E De Schutter,et al.  Precise spike timing of tactile-evoked cerebellar Golgi cell responses: a reflection of combined mossy fiber and parallel fiber activation? , 2000, Progress in brain research.

[60]  A. Gibson,et al.  Visual cells in the pontine nuclei of the cat. , 1976, The Journal of physiology.

[61]  J. F. Kalaska,et al.  Neuronal activity in primate parietal cortex area 5 varies with intended movement direction during an instructed-delay period , 2004, Experimental Brain Research.

[62]  Peter W Dicke,et al.  Characteristics of Responses of Golgi Cells and Mossy Fibers to Eye Saccades and Saccadic Adaptation Recorded from the Posterior Vermis of the Cerebellum , 2009, The Journal of Neuroscience.

[63]  G. Leichnetz,et al.  Cortical projections to the paramedian tegmental and basilar pons in the monkey , 1984, The Journal of comparative neurology.

[64]  Shigeru Tanaka,et al.  A spiking network model for passage-of-time representation in the cerebellum , 2007, The European journal of neuroscience.

[65]  T. Ebner,et al.  Position, Direction of Movement, and Speed Tuning of Cerebellar Purkinje Cells during Circular Manual Tracking in Monkey , 2005, The Journal of Neuroscience.