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Science 337 (6095): 749-753

Copyright © 2012 by the American Association for the Advancement of Science

Bergmann Glial AMPA Receptors Are Required for Fine Motor Coordination

Aiman S. Saab,1,2 Alexander Neumeyer,3,* Hannah M. Jahn,1,2,*,{dagger} Alexander Cupido,1,* Antonia A. M. Simek,4,* Henk-Jan Boele,4 Anja Scheller,1,2 Karim Le Meur,1,{ddagger} Magdalena Götz,5,6 Hannah Monyer,7 Rolf Sprengel,8 Maria E. Rubio,9 Joachim W. Deitmer,3 Chris I. De Zeeuw,4,10,§ Frank Kirchhoff1,2,§

Abstract: The impact of glial neurotransmitter receptors in vivo is still elusive. In the cerebellum, Bergmann glial (BG) cells express α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)–type glutamate receptors (AMPARs) composed exclusively of GluA1 and/or GluA4 subunits. With the use of conditional gene inactivation, we found that the majority of cerebellar GluA1/A4-type AMPARs are expressed in BG cells. In young mice, deletion of BG AMPARs resulted in retraction of glial appendages from Purkinje cell (PC) synapses, increased amplitude and duration of evoked PC currents, and a delayed formation of glutamatergic synapses. In adult mice, AMPAR inactivation also caused retraction of glial processes. The physiological and structural changes were accompanied by behavioral impairments in fine motor coordination. Thus, BG AMPARs are essential to optimize synaptic integration and cerebellar output function throughout life.

1 Department of Molecular Physiology, University of Saarland, Homburg, Germany.
2 Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
3 Fachbereich Biologie, Technische Universität Kaiserslautern, Kaiserslautern, Germany.
4 Department of Neuroscience, Erasmus MC, Rotterdam, Netherlands.
5 Department of Physiology, Ludwig-Maximilians University, Munich, Germany.
6 Institute for Stem Cell Research, Helmholtz Center Munich, Neuherberg, Germany.
7 Department of Clinical Neurobiology at the German Cancer Research Center and the Medical Faculty of the Heidelberg University, Heidelberg, Germany.
8 Department of Molecular Neurobiology, Max Planck Institute of Medical Research, Heidelberg, Germany.
9 Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA, USA.
10 Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, Netherlands.

* These authors contributed equally to this work.

{dagger} Present address: Faculty of Life Sciences, University of Manchester, Manchester, UK.

{ddagger} Present address: Systems Neuroscience, Bernstein Focus for Neurotechnology and Johann-Friedrich-Blumenbach Institut für Zoologie und Anthropologie, Georg-August-Universität Göttingen, Germany.

§ To whom correspondence should be addressed. E-mail: frank.kirchhoff{at} (F.K.); c.dezeeuw{at} (C.I.D.Z.)

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