A cerebellar learning model of vestibulo-ocular reflex adaptation in wild-type and mutant mice

TY - JOUR

T1 - A cerebellar learning model of vestibulo-ocular reflex adaptation in wild-type and mutant mice

AU - Clopath, Claudia

AU - Badura, Aleksandra

AU - De Zeeuw, Chris I

AU - Brunel, Nicolas

N1 - Copyright © 2014 the authors 0270-6474/14/347203-13$15.00/0.

PY - 2014/5/21

Y1 - 2014/5/21

N2 - Mechanisms of cerebellar motor learning are still poorly understood. The standard Marr-Albus-Ito theory posits that learning involves plasticity at the parallel fiber to Purkinje cell synapses under control of the climbing fiber input, which provides an error signal as in classical supervised learning paradigms. However, a growing body of evidence challenges this theory, in that additional sites of plasticity appear to contribute to motor adaptation. Here, we consider phase-reversal training of the vestibulo-ocular reflex (VOR), a simple form of motor learning for which a large body of experimental data is available in wild-type and mutant mice, in which the excitability of granule cells or inhibition of Purkinje cells was affected in a cell-specific fashion. We present novel electrophysiological recordings of Purkinje cell activity measured in naive wild-type mice subjected to this VOR adaptation task. We then introduce a minimal model that consists of learning at the parallel fibers to Purkinje cells with the help of the climbing fibers. Although the minimal model reproduces the behavior of the wild-type animals and is analytically tractable, it fails at reproducing the behavior of mutant mice and the electrophysiology data. Therefore, we build a detailed model involving plasticity at the parallel fibers to Purkinje cells' synapse guided by climbing fibers, feedforward inhibition of Purkinje cells, and plasticity at the mossy fiber to vestibular nuclei neuron synapse. The detailed model reproduces both the behavioral and electrophysiological data of both the wild-type and mutant mice and allows for experimentally testable predictions.

AB - Mechanisms of cerebellar motor learning are still poorly understood. The standard Marr-Albus-Ito theory posits that learning involves plasticity at the parallel fiber to Purkinje cell synapses under control of the climbing fiber input, which provides an error signal as in classical supervised learning paradigms. However, a growing body of evidence challenges this theory, in that additional sites of plasticity appear to contribute to motor adaptation. Here, we consider phase-reversal training of the vestibulo-ocular reflex (VOR), a simple form of motor learning for which a large body of experimental data is available in wild-type and mutant mice, in which the excitability of granule cells or inhibition of Purkinje cells was affected in a cell-specific fashion. We present novel electrophysiological recordings of Purkinje cell activity measured in naive wild-type mice subjected to this VOR adaptation task. We then introduce a minimal model that consists of learning at the parallel fibers to Purkinje cells with the help of the climbing fibers. Although the minimal model reproduces the behavior of the wild-type animals and is analytically tractable, it fails at reproducing the behavior of mutant mice and the electrophysiology data. Therefore, we build a detailed model involving plasticity at the parallel fibers to Purkinje cells' synapse guided by climbing fibers, feedforward inhibition of Purkinje cells, and plasticity at the mossy fiber to vestibular nuclei neuron synapse. The detailed model reproduces both the behavioral and electrophysiological data of both the wild-type and mutant mice and allows for experimentally testable predictions.

KW - Adaptation, Physiological

KW - Animals

KW - Cerebellum

KW - Computer Simulation

KW - Eye Movements

KW - Learning

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Mutant Strains

KW - Mice, Transgenic

KW - Models, Biological

KW - Mutation

KW - Nonlinear Dynamics

KW - Purkinje Cells

KW - Receptors, GABA

KW - Reflex, Vestibulo-Ocular

KW - Symporters

KW - Synapses

U2 - 10.1523/JNEUROSCI.2791-13.2014

DO - 10.1523/JNEUROSCI.2791-13.2014

M3 - Article

C2 - 24849355

SN - 0270-6474

VL - 34

SP - 7203

EP - 7215

JO - Journal of Neuroscience

JF - Journal of Neuroscience

IS - 21

ER -