Sub-processes of motor learning revealed by a robotic manipulandum for rodents

Rodent models are widely used to investigate neural changes in response to motor learning. Usually, the behavioral readout of motor learning tasks used for this purpose is restricted to a binary measure of performance (i.e. "successful" movement vs. "failure"). Thus, the assignability of research in rodents to concepts gained in human research - implying diverse internal models that constitute motor learning - is still limited. To solve this problem, we recently introduced a three-degree-of-freedom robotic platform designed for rats (the ETH-Pattus) that combines an accurate behavioral readout (in the form of kinematics) with the possibility to invasively assess learning related changes within the brain (e.g. by performing immunohistochemistry or electrophysiology in acute slice preparations). Here, we validate this platform as a tool to study motor learning by establishing two forelimb-reaching paradigms that differ in degree of skill. Both conditions can be precisely differentiated in terms of their temporal pattern and performance levels. Based on behavioral data, we hypothesize the presence of several sub-processes contributing to motor learning. These share close similarities with concepts gained in humans or primates.

[1]  S. Micera,et al.  A Robotic System for Quantitative Assessment and Poststroke Training of Forelimb Retraction in Mice , 2014, Neurorehabilitation and neural repair.

[2]  Ian Q Whishaw,et al.  The pasta matrix reaching task: a simple test for measuring skilled reaching distance, direction, and dexterity in rats , 2001, Journal of Neuroscience Methods.

[3]  O. Hikosaka,et al.  Transition of Brain Activation from Frontal to Parietal Areas in Visuomotor Sequence Learning , 1998, The Journal of Neuroscience.

[4]  Ian Q. Whishaw,et al.  The structure of skilled forelimb reaching in the rat: A proximally driven movement with a single distal rotatory component , 1990, Behavioural Brain Research.

[5]  Helen J. Huang,et al.  Reduction of Metabolic Cost during Motor Learning of Arm Reaching Dynamics , 2012, The Journal of Neuroscience.

[6]  J. Krakauer,et al.  How is a motor skill learned? Change and invariance at the levels of task success and trajectory control. , 2012, Journal of neurophysiology.

[7]  Willie F. Tobin,et al.  Rapid formation and selective stabilization of synapses for enduring motor memories , 2009, Nature.

[8]  Ethan R. Buch,et al.  Noninvasive cortical stimulation enhances motor skill acquisition over multiple days through an effect on consolidation , 2009, Proceedings of the National Academy of Sciences.

[9]  Andreas R. Luft,et al.  Characterization of motor skill and instrumental learning time scales in a skilled reaching task in rat , 2004, Behavioural Brain Research.

[10]  Andreas R Luft,et al.  Short and long-term motor skill learning in an accelerated rotarod training paradigm , 2004, Neurobiology of Learning and Memory.

[11]  N. Hogan,et al.  Submovements grow larger, fewer, and more blended during stroke recovery. , 2003, Motor control.

[12]  Joseph T. Francis,et al.  Force field apparatus for investigating movement control in small animals , 2004, IEEE Transactions on Biomedical Engineering.

[13]  J. Donoghue,et al.  Learning-induced LTP in neocortex. , 2000, Science.

[14]  O. Hikosaka,et al.  Learning of sequential movements in the monkey: process of learning and retention of memory. , 1995, Journal of neurophysiology.

[15]  J. Kleim,et al.  Functional reorganization of the rat motor cortex following motor skill learning. , 1998, Journal of neurophysiology.

[16]  Jaime E. Duarte,et al.  Effort, performance, and motivation: Insights from robot-assisted training of human golf putting and rat grip strength , 2013, 2013 IEEE 13th International Conference on Rehabilitation Robotics (ICORR).

[17]  Bence P Ölveczky,et al.  Motoring ahead with rodents , 2011, Current Opinion in Neurobiology.

[18]  R. Nudo,et al.  3.21 – Neurophysiology of Motor Skill Learning , 2008 .

[19]  Lori-Ann R. Sacrey,et al.  The use of rodent skilled reaching as a translational model for investigating brain damage and disease , 2012, Neuroscience & Biobehavioral Reviews.

[20]  Michael I. Jordan,et al.  Optimal feedback control as a theory of motor coordination , 2002, Nature Neuroscience.

[21]  T. Milner,et al.  A model for the generation of movements requiring endpoint precision , 1992, Neuroscience.

[22]  J. Larson,et al.  Effects of unilateral and bilateral training in a reaching task on dendritic branching of neurons in the rat motor-sensory forelimb cortex. , 1985, Behavioral and neural biology.

[23]  C. Hofsten,et al.  Structuring of early reaching movements: a longitudinal study. , 1991 .

[24]  Etienne Burdet,et al.  Quantization of human motions and learning of accurate movements , 1998, Biological Cybernetics.

[25]  Ian Q. Whishaw,et al.  The impairments in reaching and the movements of compensation in rats with motor cortex lesions: an endpoint, videorecording, and movement notation analysis , 1991, Behavioural Brain Research.

[26]  Ling Wang,et al.  Structural plasticity within highly specific neuronal populations identifies a unique parcellation of motor learning in the adult brain , 2011, Proceedings of the National Academy of Sciences.

[27]  M. Calhoun,et al.  Region and task-specific activation of Arc in primary motor cortex of rats following motor skill learning , 2013, Neuroscience.

[28]  R. Bogacz,et al.  The neural basis of the speed–accuracy tradeoff , 2010, Trends in Neurosciences.

[29]  T. Flash,et al.  The coordination of arm movements: an experimentally confirmed mathematical model , 1985, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[30]  M. Willingham,et al.  Prognostic significance of Bcl‐2 in Wilms' tumor and oncogenic potential of Bcl‐XL in rare tumor cases , 1999, International journal of cancer.

[31]  F A Mussa-Ivaldi,et al.  Adaptive representation of dynamics during learning of a motor task , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[32]  J. Kleim,et al.  Synaptogenesis and FOS Expression in the Motor Cortex of the Adult Rat after Motor Skill Learning , 1996, The Journal of Neuroscience.

[33]  L. Squire Memory systems of the brain: A brief history and current perspective , 2004, Neurobiology of Learning and Memory.

[34]  A. Luft,et al.  Stages of motor skill learning , 2005, Molecular Neurobiology.

[35]  Olivier Lambercy,et al.  A Robotic Platform to Assess, Guide and Perturb Rat Forelimb Movements , 2013, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[36]  Olivier Lambercy,et al.  A small-scale robotic manipulandum for motor training in stroke rats , 2011, 2011 IEEE International Conference on Rehabilitation Robotics.

[37]  Andreas R. Luft,et al.  Motor learning transiently changes cortical somatotopy , 2008, NeuroImage.

[38]  Kae Nakamura,et al.  Central mechanisms of motor skill learning , 2002, Current Opinion in Neurobiology.

[39]  J. Krakauer,et al.  Human sensorimotor learning: adaptation, skill, and beyond , 2011, Current Opinion in Neurobiology.

[40]  I. Whishaw An endpoint, descriptive, and kinematic comparison of skilled reaching in mice (Mus musculus) with rats (Rattus norvegicus) , 1996, Behavioural Brain Research.

[41]  Theresa A. Jones,et al.  The Vermicelli Handling Test: A simple quantitative measure of dexterous forepaw function in rats , 2008, Journal of Neuroscience Methods.

[42]  Stephen C. Fowler,et al.  Unlike haloperidol, clozapine slows and dampens rats' forelimb force oscillations and decreases force output in a press-while-licking behavioral task , 2005, Psychopharmacology.