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The Journal of Neuroscience, April 15, 2003, 23(8):3469

Calbindin in Cerebellar Purkinje Cells Is a Critical Determinant of the Precision of Motor Coordination

Jaroslaw J. Barski^{1, 2}, Jana Hartmann³, Christine R. Rose³, Freek Hoebeek⁴, Karin Mörl¹, Michael Noll-Hussong³, Chris I. De Zeeuw⁴, Arthur Konnerth³, and Michael Meyer^{1, 2}

¹ Max-Planck-Institute of Neurobiology, D-82152 Martinsried, Germany, ² Institute of Ophthalmology, University College London, London EC1V 9EL, United Kingdom, ³ Institute of Physiology, Ludwig-Maximilians-University of Munich, D-80336 Munich, Germany, and ⁴ Department of Neuroscience, Erasmus University Rotterdam, 3000DR Rotterdam, The Netherlands

Long-term depression (LTD) of Purkinje cell-parallel fiber synaptic transmission is a critical determinant of normal cerebellar function. Impairment of LTD through, for example, disruption of the metabotropic glutamate receptor-IP₃-calcium signaling cascade in mutant mice results in severe deficits of both synaptic transmission and cerebellar motor control. Here, we demonstrate that selective genetic deletion of the calcium-binding protein calbindin D-28k (calbindin) from cerebellar Purkinje cells results in distinctly different cellular and behavioral alterations. These mutants display marked permanent deficits of motor coordination and sensory processing. This occurs in the absence of alterations in a form of LTD implicated in the control of behavior. Analysis of synaptically evoked calcium transients in spines and dendrites of Purkinje cells demonstrated an alteration of time course and amplitude of fast calcium transients after parallel or climbing fiber stimulation. By contrast, the delayed metabotropic glutamate receptor-mediated calcium transients were normal. Our results reveal a unique role of Purkinje cell calbindin in a specific form of motor control and suggest that rapid calcium buffering may directly control behaviorally relevant neuronal signal integration.

Key words: calbindin D-28k; conditional null mutant; Purkinje cell; motor coordination; long-term depression; synaptically evoked calcium transients

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Copyright © 2003 Society for Neuroscience  0270-6474/03/2383469-09$05.00/0

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