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

dc.contributor.author

Clopath, Claudia

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Badura, Aleksandra

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De Zeeuw, Chris I

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Brunel, Nicolas

dc.date.accessioned

2021-06-06T16:27:24Z

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2021-06-06T16:27:24Z

dc.date.issued

2014-05

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2021-06-06T16:27:23Z

dc.description.abstract

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.

dc.identifier

34/21/7203

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0270-6474

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1529-2401

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https://hdl.handle.net/10161/23358

dc.language

eng

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Society for Neuroscience

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The Journal of neuroscience : the official journal of the Society for Neuroscience

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10.1523/jneurosci.2791-13.2014

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Cerebellum

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Purkinje Cells

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Synapses

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Animals

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Mice, Inbred C57BL

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Mice, Transgenic

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Mice

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Mice, Mutant Strains

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Symporters

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Receptors, GABA

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Eye Movements

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Learning

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Adaptation, Physiological

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Reflex, Vestibulo-Ocular

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Mutation

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Nonlinear Dynamics

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Models, Biological

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Computer Simulation

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Male

dc.title

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

dc.type

Journal article

duke.contributor.orcid

Brunel, Nicolas|0000-0002-2272-3248

pubs.begin-page

7203

pubs.end-page

7215

pubs.issue

21

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School of Medicine

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Physics

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Neurobiology

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Duke Institute for Brain Sciences

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Center for Cognitive Neuroscience

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Duke

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Trinity College of Arts & Sciences

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Basic Science Departments

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University Institutes and Centers

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Institutes and Provost's Academic Units

pubs.publication-status

Published

pubs.volume

34

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