Multiple components in direction learning in smooth pursuit eye movements of monkeys.

We analyzed behavioral features of smooth pursuit eye movements to characterize the course of acquisition and expression of multiple neural components of motor learning. Monkeys tracked a target that began to move in an initial "pursuit" direction and suddenly, but predictably, changed direction after a fixed interval of 250 ms. As the trial is repeated, monkeys learn to make eye movements that predict the change in target direction. Quantitative analysis of the learned response revealed evidence for multiple, dynamic, parallel processes at work during learning. 1) The overall learning followed at least two trial courses: a fast component grew and saturated rapidly over tens of trials, and a slow component grew steadily over up to 1,000 trials. 2) The temporal specificity of the learned response within each trial was crude during the first 100 trials but then improved gradually over the remaining trials. 3) External influences on the gain of pursuit initiation modulate the expression but probably not the acquisition of learning. The gain of pursuit initiation and the expression of the learned response decreased in parallel, both gradually through a 1,000-trial learning block and immediately between learning trials with different gains in the initiation of pursuit. We conclude that at least two distinct neural mechanisms drive the acquisition of pursuit learning over 100 to 1,000 trials (3 to 30 min). Both mechanisms generate underlying memory traces that are modulated in relation to the gain of pursuit initiation before expression in the final motor output. NEW & NOTEWORTHY We show that cerebellum-dependent direction learning in smooth pursuit eye movements grows in at least two components over 1,100 behavioral learning repetitions. One component grows over tens of trials and the other over hundreds. Within trials, learned temporal specificity gradually improves over hundreds of trials. The expression of each learning component on a given trial can be modified by external factors that do not affect the underlying memory trace.

[1]  Stephen G Lisberger,et al.  Reward Action in the Initiation of Smooth Pursuit Eye Movements , 2012, The Journal of Neuroscience.

[2]  R. Shadmehr,et al.  Spontaneous recovery of motor memory during saccade adaptation. , 2008, Journal of neurophysiology.

[3]  Stephen G. Lisberger,et al.  Signal, Noise, and Variation in Neural and Sensory-Motor Latency , 2016, Neuron.

[4]  G. Hesslow,et al.  Acquisition, Extinction, and Reacquisition of a Cerebellar Cortical Memory Trace , 2007, The Journal of Neuroscience.

[5]  Javier F. Medina,et al.  Timing Mechanisms in the Cerebellum: Testing Predictions of a Large-Scale Computer Simulation , 2000, The Journal of Neuroscience.

[6]  Michael D Mauk,et al.  A Subtraction Mechanism of Temporal Coding in Cerebellar Cortex , 2011, The Journal of Neuroscience.

[7]  D J Krupa,et al.  Inactivation of the superior cerebellar peduncle blocks expression but not acquisition of the rabbit's classically conditioned eye-blink response. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[8]  Richard F. Thompson,et al.  Localization of a memory trace in the mammalian brain. , 1993, Science.

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

[10]  A. Fuchs,et al.  Eye movements evoked by stimulation of frontal eye fields. , 1969, Journal of neurophysiology.

[11]  Stephen G. Lisberger,et al.  The Representation of Time for Motor Learning , 2005, Neuron.

[12]  Megan R. Carey,et al.  Synaptic mechanisms of sensorimotor learning in the cerebellum , 2011, Current Opinion in Neurobiology.

[13]  Martijn Schonewille,et al.  Mechanisms underlying vestibulo‐cerebellar motor learning in mice depend on movement direction , 2017, The Journal of physiology.

[14]  I. Gormezano,et al.  Acquisition and Extinction of the Classically Conditioned Eyelid Response in the Albino Rabbit , 1962, Science.

[15]  R. Shadmehr,et al.  Interacting Adaptive Processes with Different Timescales Underlie Short-Term Motor Learning , 2006, PLoS biology.

[16]  S G Lisberger,et al.  Behavioral Analysis of Signals that Guide Learned Changes in the Amplitude and Dynamics of the Vestibulo-Ocular Reflex , 1996, The Journal of Neuroscience.

[17]  Dominique L. Pritchett,et al.  Locomotor activity modulates associative learning in mouse cerebellum , 2017, Nature Neuroscience.

[18]  D. M. Broussard,et al.  The Site of a Motor Memory Shifts with Consolidation , 2005, The Journal of Neuroscience.

[19]  Stephen G Lisberger,et al.  Encoding and decoding of learned smooth-pursuit eye movements in the floccular complex of the monkey cerebellum. , 2009, Journal of neurophysiology.

[20]  Richard F. Thompson,et al.  Neural substrates of eyeblink conditioning: acquisition and retention. , 2003, Learning & memory.

[21]  S. Lisberger,et al.  Neural basis for motor learning in the vestibuloocular reflex of primates. I. Changes in the responses of brain stem neurons. , 1994, Journal of neurophysiology.

[22]  C. Rashbass,et al.  The relationship between saccadic and smooth tracking eye movements , 1961, The Journal of physiology.

[23]  S G Lisberger,et al.  Changes in the responses of Purkinje cells in the floccular complex of monkeys after motor learning in smooth pursuit eye movements. , 2000, Journal of neurophysiology.

[24]  Stephen G Lisberger,et al.  Role of Plasticity at Different Sites across the Time Course of Cerebellar Motor Learning , 2014, The Journal of Neuroscience.

[25]  N. Schweighofer,et al.  Dual Adaptation Supports a Parallel Architecture of Motor Memory , 2009, The Journal of Neuroscience.

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

[27]  P. W. Frey,et al.  Classical conditioning of the rabbit eyelid response as a function of interstimulus interval. , 1968, Journal of comparative and physiological psychology.

[28]  Michael D Mauk,et al.  Cerebellar cortex contributions to the expression and timing of conditioned eyelid responses. , 2010, Journal of neurophysiology.

[29]  M. Mauk,et al.  Learning-Induced Plasticity in Deep Cerebellar Nucleus , 2006, The Journal of Neuroscience.

[30]  F. A. Miles,et al.  Plasticity in the vestibulo-ocular reflex: a new hypothesis. , 1981, Annual review of neuroscience.

[31]  S. Lisberger.  Neural basis for motor learning in the vestibuloocular reflex of primates. III. Computational and behavioral analysis of the sites of learning. , 1994, Journal of neurophysiology.

[32]  Stephen G Lisberger,et al.  Interaction of plasticity and circuit organization during the acquisition of cerebellum-dependent motor learning , 2013, eLife.

[33]  F A Miles,et al.  Long-term adaptive changes in primate vestibuloocular reflex. I. Behavioral observations. , 1980, Journal of neurophysiology.

[34]  E. Kehoe,et al.  Rapid reacquisition in conditioning of the rabbit's nictitating membrane response. , 1992 .

[35]  Kaoru Yoshida,et al.  Memory of Learning Facilitates Saccadic Adaptation in the Monkey , 2004, The Journal of Neuroscience.

[36]  S. Lisberger,et al.  Normal performance and expression of learning in the vestibulo-ocular reflex (VOR) at high frequencies. , 2005, Journal of neurophysiology.

[37]  Stephen G Lisberger,et al.  Learning on multiple timescales in smooth pursuit eye movements. , 2010, Journal of neurophysiology.

[38]  A. Fuchs,et al.  Role of primate flocculus during rapid behavioral modification of vestibuloocular reflex. I. Purkinje cell activity during visually guided horizontal smooth-pursuit eye movements and passive head rotation. , 1978, Journal of neurophysiology.

[39]  Rhea R. Kimpo,et al.  Gating of neural error signals during motor learning , 2014, eLife.

[40]  E. D’Angelo,et al.  Beyond parallel fiber LTD: the diversity of synaptic and non-synaptic plasticity in the cerebellum , 2001, Nature Neuroscience.

[41]  P. Strata,et al.  Cerebellum: history , 2009, Neuroscience.

[42]  J. Raymond,et al.  Elimination of climbing fiber instructive signals during motor learning , 2009, Nature Neuroscience.

[43]  Richard F. Thompson.  An essential memory trace found. , 2013, Behavioral neuroscience.

[44]  Links from complex spikes to local plasticity and motor learning in the cerebellum of awake-behaving monkeys. , 2008, Nature neuroscience.

[45]  E. Boyden,et al.  Cerebellum-dependent learning: the role of multiple plasticity mechanisms. , 2004, Annual review of neuroscience.

[46]  S. Lisberger,et al.  Visual responses of Purkinje cells in the cerebellar flocculus during smooth-pursuit eye movements in monkeys. I. Simple spikes. , 1990, Journal of neurophysiology.

[47]  W. T. Thach,et al.  Purkinje cell activity during motor learning , 1977, Brain Research.

[48]  M. Mauk,et al.  Cerebellar cortex lesions disrupt learning-dependent timing of conditioned eyelid responses , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.