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Deletion of the GluRδ2 Receptor in the Hotfoot Mouse Mutant Causes Granule Cell Loss, Delayed Purkinje Cell Death, and Reductions in Purkinje Cell Dendritic Tree Area

Authors
  • Zanjani, Hadi S.1, 2
  • Vogel, Michael W.3
  • Mariani, Jean1, 2, 4
  • 1 Sorbonne Universités UPMC Univ. Paris 06, IBPS, UMR 8256, Biological Adaptation and Ageing, B2A, Paris, 75005, France , Paris (France)
  • 2 CNRS, UMR 8256, B2A, Paris, F-75005, France , Paris (France)
  • 3 University of Maryland School of Medicine, Maryland Psychiatric Research Center, Department of Psychiatry, Baltimore, MD, 21228, USA , Baltimore (United States)
  • 4 Institut de la Longévité, APHP, DHU Fast, Ivry-Sur-Seine, 94205, France , Ivry-Sur-Seine (France)
Type
Published Article
Journal
The Cerebellum
Publisher
Springer US
Publication Date
Nov 25, 2015
Volume
15
Issue
6
Pages
755–766
Identifiers
DOI: 10.1007/s12311-015-0748-7
Source
Springer Nature
Keywords
License
Yellow

Abstract

Recent studies have found that in the cerebellum, the δ2 glutamate receptor (GluRδ2) plays a key role in regulating the differentiation of parallel fiber-Purkinje synapses and mediating key physiological functions in the granule cell-Purkinje cell circuit. In the hotfoot mutant or GluRδ2 knockout mice, the absence of GluRδ2 expression results in impaired motor-related tasks, ataxia, and disruption of long-term depression at parallel fiber-Purkinje cell synapses. The goal of this study was to determine the long-term consequences of deletion of GluRδ2 expression in the hotfoot mutant (GluRδ2ho/ho) on Purkinje and granule cell survival and Purkinje cell dendritic differentiation. Quantitative estimates of Purkinje and granule cell numbers in 3-, 12-, and 20-month-old hotfoot mutants and wild-type controls showed that Purkinje cell numbers are within control values at 3 and 12 months in the hotfoot mutant but reduced by 20 % at 20 months compared with controls. In contrast, the number of granule cells is significantly reduced from 3 months onwards in GluRδ2ho/ho mutant mice compared to wild-type controls. Although the overall structure of Purkinje cell dendrites does not appear to be altered, there is a significant 27 % reduction in the cross-sectional area of Purkinje cell dendritic trees in the 20-month-old GluRδ2ho/ho mutants. The interpretation of the results is that the GluRδ2 receptor plays an important role in the long-term organization of the granule-Purkinje cell circuit through its involvement in the regulation of parallel fiber-Purkinje cell synaptogenesis and in the normal functioning of this critical cerebellar circuit.

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