Affordable Access

Access to the full text

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

  • 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)
Published Article
The Cerebellum
Springer US
Publication Date
Nov 25, 2015
DOI: 10.1007/s12311-015-0748-7
Springer Nature


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.

Report this publication


Seen <100 times