Expression of a protein kinase C inhibitor in purkinje cells blocks cerebellar LTD and adaptation of the vestibulo-ocular reflex

Chris I. De Zeeuw, Christian Hansel, Feng Bian, Sebastiaan K E Koekkoek, Adriaan M. Van Alphen, David J Linden, John Oberdick

Research output: Contribution to journalArticle

Abstract

Cerebellar long-term depression (LTD) is a model system for neuronal information storage that has an absolute requirement for activation of protein kinase C (PKC). It has been claimed to underlie several forms of cerebellar motor learning. Previous studies using various knockout mice (mGluR1, GluRδ2, glial fibrillary acidic protein) have supported this claim; however, this work has suffered from the limitations that the knockout technique lacks anatomical specificity and that functional compensation can occur via similar gene family members. To overcome these limitations, a transgenic mouse (called L7-PKCI) has been produced in which the pseudosubstrate PKC inhibitor, PKC[19-31], was selectively expressed in Purkinje cells under the control of the pcp-2(L7) gene promoter. Cultured Purkinje cells prepared from heterozygous or homozygous L7-PKCI embryos showed a complete blockade of LTD induction. In addition, the compensatory eye movements of L7-PKCI mice were recorded during vestibular and visual stimulation. Whereas the absolute gain, phase, and latency values of the vestibulo-ocular reflex and optokinetic reflex of the L7-PKCI mice were normal, their ability to adapt their vestibulo-ocular reflex gain during visuo-vestibular training was absent. These data strongly support the hypothesis that activation of PKC in the Purkinje cell is necessary for cerebellar LTD induction, and that cerebellar LTD is required for a particular form of motor learning, adaptation of the vestibulo-ocular reflex.

Original languageEnglish (US)
Pages (from-to)495-508
Number of pages14
JournalNeuron
Volume20
Issue number3
DOIs
StatePublished - Mar 1998

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Vestibulo-Ocular Reflex
Protein C Inhibitor
Purkinje Cells
Protein Kinase Inhibitors
Protein Kinase C
Depression
Learning
Photic Stimulation
Aptitude
Information Storage and Retrieval
Glial Fibrillary Acidic Protein
Eye Movements
Knockout Mice
Transgenic Mice
Genes
Reflex
Cultured Cells
Embryonic Structures

ASJC Scopus subject areas

  • Neuroscience(all)

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Expression of a protein kinase C inhibitor in purkinje cells blocks cerebellar LTD and adaptation of the vestibulo-ocular reflex. / De Zeeuw, Chris I.; Hansel, Christian; Bian, Feng; Koekkoek, Sebastiaan K E; Van Alphen, Adriaan M.; Linden, David J; Oberdick, John.

In: Neuron, Vol. 20, No. 3, 03.1998, p. 495-508.

Research output: Contribution to journalArticle

De Zeeuw, Chris I. ; Hansel, Christian ; Bian, Feng ; Koekkoek, Sebastiaan K E ; Van Alphen, Adriaan M. ; Linden, David J ; Oberdick, John. / Expression of a protein kinase C inhibitor in purkinje cells blocks cerebellar LTD and adaptation of the vestibulo-ocular reflex. In: Neuron. 1998 ; Vol. 20, No. 3. pp. 495-508.
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