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

Overview

Journal J Neurosci

Specialty Neurology

Date 2003 Apr 30

PMID 12716955

Citations 81

Authors

Jaroslaw J Barski

Jana Hartmann

Christine R Rose

Freek Hoebeek

Karin Morl

Michael Noll-Hussong

Chris I De Zeeuw

Arthur Konnerth

Michael Meyer

Affiliations

Soon will be listed here.

Abstract

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.

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References

Maeda H, Ito K, Miyashita Y, Kasai H . Supralinear Ca2+ signaling by cooperative and mobile Ca2+ buffering in Purkinje neurons. Neuron. 2000; 24(4):989-1002. DOI: 10.1016/s0896-6273(00)81045-4. View

Ichise T, Kano M, Hashimoto K, Yanagihara D, Nakao K, Shigemoto R . mGluR1 in cerebellar Purkinje cells essential for long-term depression, synapse elimination, and motor coordination. Science. 2000; 288(5472):1832-5. DOI: 10.1126/science.288.5472.1832. View

Caillard O, Moreno H, Schwaller B, Llano I, Celio M, Marty A . Role of the calcium-binding protein parvalbumin in short-term synaptic plasticity. Proc Natl Acad Sci U S A. 2000; 97(24):13372-7. PMC: 27231. DOI: 10.1073/pnas.230362997. View

Miyata M, Finch E, Khiroug L, Hashimoto K, Hayasaka S, Oda S . Local calcium release in dendritic spines required for long-term synaptic depression. Neuron. 2000; 28(1):233-44. DOI: 10.1016/s0896-6273(00)00099-4. View

Wang S, Denk W, Hausser M . Coincidence detection in single dendritic spines mediated by calcium release. Nat Neurosci. 2000; 3(12):1266-73. DOI: 10.1038/81792. View

Barski J, Dethleffsen K, Meyer M . Cre recombinase expression in cerebellar Purkinje cells. Genesis. 2000; 28(3-4):93-8. View

Ito M . Cerebellar long-term depression: characterization, signal transduction, and functional roles. Physiol Rev. 2001; 81(3):1143-95. DOI: 10.1152/physrev.2001.81.3.1143. View

Goossens J, Daniel H, Rancillac A, van der Steen J, Oberdick J, Crepel F . Expression of protein kinase C inhibitor blocks cerebellar long-term depression without affecting Purkinje cell excitability in alert mice. J Neurosci. 2001; 21(15):5813-23. PMC: 6762649. View

Rose C, Konnerth A . Stores not just for storage. intracellular calcium release and synaptic plasticity. Neuron. 2001; 31(4):519-22. DOI: 10.1016/s0896-6273(01)00402-0. View

10.

Barski J, Morl K, Meyer M . Conditional inactivation of the calbindin D-28k (Calb1) gene by Cre/loxP-mediated recombination. Genesis. 2002; 32(2):165-8. DOI: 10.1002/gene.10045. View

11.

Lev-Ram V, Wong S, Storm D, Tsien R . A new form of cerebellar long-term potentiation is postsynaptic and depends on nitric oxide but not cAMP. Proc Natl Acad Sci U S A. 2002; 99(12):8389-93. PMC: 123077. DOI: 10.1073/pnas.122206399. View

12.

van Alphen A, de Zeeuw C . Cerebellar LTD facilitates but is not essential for long-term adaptation of the vestibulo-ocular reflex. Eur J Neurosci. 2002; 16(3):486-90. DOI: 10.1046/j.1460-9568.2002.02094.x. View

13.

Konnerth A, Dreessen J, Augustine G . Brief dendritic calcium signals initiate long-lasting synaptic depression in cerebellar Purkinje cells. Proc Natl Acad Sci U S A. 1992; 89(15):7051-5. PMC: 49643. DOI: 10.1073/pnas.89.15.7051. View

14.

Martin L, Blackstone C, Huganir R, Price D . Cellular localization of a metabotropic glutamate receptor in rat brain. Neuron. 1992; 9(2):259-70. DOI: 10.1016/0896-6273(92)90165-a. View

15.

Pochet R, Pasteels B, Bastianelli E, Kitajima S, Van Eldik L . Calmodulin and calbindin localization in retina from six vertebrate species. J Comp Neurol. 1991; 314(4):750-62. DOI: 10.1002/cne.903140408. View

16.

Konnerth A, Llano I, ARMSTRONG C . Synaptic currents in cerebellar Purkinje cells. Proc Natl Acad Sci U S A. 1990; 87(7):2662-5. PMC: 53750. DOI: 10.1073/pnas.87.7.2662. View

17.

Sakurai M . Calcium is an intracellular mediator of the climbing fiber in induction of cerebellar long-term depression. Proc Natl Acad Sci U S A. 1990; 87(9):3383-5. PMC: 53904. DOI: 10.1073/pnas.87.9.3383. View

18.

Celio M . Calbindin D-28k and parvalbumin in the rat nervous system. Neuroscience. 1990; 35(2):375-475. DOI: 10.1016/0306-4522(90)90091-h. View

19.

Passingham R, Myers C, Rawlins N, Lightfoot V, Fearn S . Premotor cortex in the rat. Behav Neurosci. 1988; 102(1):101-9. DOI: 10.1037//0735-7044.102.1.101. View

20.

Ito M . Long-term depression as a memory process in the cerebellum. Neurosci Res. 1986; 3(6):531-9. DOI: 10.1016/0168-0102(86)90052-0. View