Reevaluating the role of LTD in cerebellar motor learning

Martijn Schonewille; Zhenyu Gao; Henk-Jan Boele; Maria F Vinueza Veloz; Wardell E Amerika; Antonia A M Simek; Marcel T De Jeu; Jordan P Steinberg; Kogo Takamiya; Freek E Hoebeek; David J Linden; Richard L Huganir; Chris I De Zeeuw

doi:10.1016/j.neuron.2011.02.044

Reevaluating the role of LTD in cerebellar motor learning

Martijn Schonewille, Zhenyu Gao, Henk-Jan Boele, Maria F Vinueza Veloz, Wardell E Amerika, Antonia A M Simek, Marcel T De Jeu, Jordan P Steinberg, Kogo Takamiya, Freek E Hoebeek, David J Linden, Richard L Huganir, Chris I De Zeeuw

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Long-term depression at parallel fiber-Purkinje cell synapses (PF-PC LTD) has been proposed to be required for cerebellar motor learning. To date, tests of this hypothesis have sought to interfere with receptors (mGluR1) and enzymes (PKC, PKG, or αCamKII) necessary for induction of PF-PC LTD and thereby determine if cerebellar motor learning is impaired. Here, we tested three mutant mice that target the expression of PF-PC LTD by blocking internalization of AMPA receptors. Using three different cerebellar coordination tasks (adaptation of the vestibulo-ocular reflex, eyeblink conditioning, and locomotion learning on the Erasmus Ladder), we show that there is no motor learning impairment in these mutant mice that lack PF-PC LTD. These findings demonstrate that PF-PC LTD is not essential for cerebellar motor learning.

Original language	English
Pages (from-to)	43-50
Number of pages	8
Journal	Neuron
Volume	70
Issue number	1
DOIs	https://doi.org/10.1016/j.neuron.2011.02.044
Publication status	Published - 14 Apr 2011
Externally published	Yes

Keywords

Animals
Blinking/physiology
Cerebellum/physiology
Gene Knock-In Techniques
Learning/physiology
Long-Term Synaptic Depression/physiology
Mice
Mice, Knockout
Motor Activity/physiology
Nerve Net/physiology
Neuronal Plasticity/physiology
Reflex, Vestibulo-Ocular/physiology

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10.1016/j.neuron.2011.02.044

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title = "Reevaluating the role of LTD in cerebellar motor learning",

abstract = "Long-term depression at parallel fiber-Purkinje cell synapses (PF-PC LTD) has been proposed to be required for cerebellar motor learning. To date, tests of this hypothesis have sought to interfere with receptors (mGluR1) and enzymes (PKC, PKG, or αCamKII) necessary for induction of PF-PC LTD and thereby determine if cerebellar motor learning is impaired. Here, we tested three mutant mice that target the expression of PF-PC LTD by blocking internalization of AMPA receptors. Using three different cerebellar coordination tasks (adaptation of the vestibulo-ocular reflex, eyeblink conditioning, and locomotion learning on the Erasmus Ladder), we show that there is no motor learning impairment in these mutant mice that lack PF-PC LTD. These findings demonstrate that PF-PC LTD is not essential for cerebellar motor learning.",

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author = "Martijn Schonewille and Zhenyu Gao and Henk-Jan Boele and Veloz, {Maria F Vinueza} and Amerika, {Wardell E} and Simek, {Antonia A M} and {De Jeu}, {Marcel T} and Steinberg, {Jordan P} and Kogo Takamiya and Hoebeek, {Freek E} and Linden, {David J} and Huganir, {Richard L} and {De Zeeuw}, {Chris I}",

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AU - Schonewille, Martijn

AU - Gao, Zhenyu

AU - Boele, Henk-Jan

AU - Veloz, Maria F Vinueza

AU - Amerika, Wardell E

AU - Simek, Antonia A M

AU - De Jeu, Marcel T

AU - Steinberg, Jordan P

AU - Takamiya, Kogo

AU - Hoebeek, Freek E

AU - Linden, David J

AU - Huganir, Richard L

AU - De Zeeuw, Chris I

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N2 - Long-term depression at parallel fiber-Purkinje cell synapses (PF-PC LTD) has been proposed to be required for cerebellar motor learning. To date, tests of this hypothesis have sought to interfere with receptors (mGluR1) and enzymes (PKC, PKG, or αCamKII) necessary for induction of PF-PC LTD and thereby determine if cerebellar motor learning is impaired. Here, we tested three mutant mice that target the expression of PF-PC LTD by blocking internalization of AMPA receptors. Using three different cerebellar coordination tasks (adaptation of the vestibulo-ocular reflex, eyeblink conditioning, and locomotion learning on the Erasmus Ladder), we show that there is no motor learning impairment in these mutant mice that lack PF-PC LTD. These findings demonstrate that PF-PC LTD is not essential for cerebellar motor learning.

AB - Long-term depression at parallel fiber-Purkinje cell synapses (PF-PC LTD) has been proposed to be required for cerebellar motor learning. To date, tests of this hypothesis have sought to interfere with receptors (mGluR1) and enzymes (PKC, PKG, or αCamKII) necessary for induction of PF-PC LTD and thereby determine if cerebellar motor learning is impaired. Here, we tested three mutant mice that target the expression of PF-PC LTD by blocking internalization of AMPA receptors. Using three different cerebellar coordination tasks (adaptation of the vestibulo-ocular reflex, eyeblink conditioning, and locomotion learning on the Erasmus Ladder), we show that there is no motor learning impairment in these mutant mice that lack PF-PC LTD. These findings demonstrate that PF-PC LTD is not essential for cerebellar motor learning.

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KW - Cerebellum/physiology

KW - Gene Knock-In Techniques

KW - Learning/physiology

KW - Long-Term Synaptic Depression/physiology

KW - Mice

KW - Mice, Knockout

KW - Motor Activity/physiology

KW - Nerve Net/physiology

KW - Neuronal Plasticity/physiology

KW - Reflex, Vestibulo-Ocular/physiology

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DO - 10.1016/j.neuron.2011.02.044

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VL - 70

SP - 43

EP - 50

JO - Neuron

JF - Neuron

IS - 1

ER -

Reevaluating the role of LTD in cerebellar motor learning

Abstract

Keywords

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