A cerebellar learning model of vestibulo-ocular reflex adaptation in wild-type and mutant mice.
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.
Type
Journal articleSubject
CerebellumPurkinje Cells
Synapses
Animals
Mice, Inbred C57BL
Mice, Transgenic
Mice
Mice, Mutant Strains
Symporters
Receptors, GABA
Eye Movements
Learning
Adaptation, Physiological
Reflex, Vestibulo-Ocular
Mutation
Nonlinear Dynamics
Models, Biological
Computer Simulation
Male
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https://hdl.handle.net/10161/23358Published Version (Please cite this version)
10.1523/jneurosci.2791-13.2014Publication Info
Clopath, Claudia; Badura, Aleksandra; De Zeeuw, Chris I; & Brunel, Nicolas (2014). A cerebellar learning model of vestibulo-ocular reflex adaptation in wild-type and
mutant mice. The Journal of neuroscience : the official journal of the Society for Neuroscience, 34(21). pp. 7203-7215. 10.1523/jneurosci.2791-13.2014. Retrieved from https://hdl.handle.net/10161/23358.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Nicolas Brunel
Duke School of Medicine Distinguished Professor in Neuroscience
We use theoretical models of brain systems to investigate how they process and learn
information from their inputs. Our current work focuses on the mechanisms of learning
and memory, from the synapse to the network level, in collaboration with various experimental
groups. Using methods fromstatistical physics, we have shown recently that the synapticconnectivity
of a network that maximizes storage capacity reproducestwo key experimentally observed
features: low connection proba

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