title: 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.
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/homutant 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/homutants. 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.
authors.affiliation: Sorbonne Universités UPMC Univ. Paris 06, IBPS, UMR 8256, Biological Adaptation and Ageing, B2A, 75005, Paris, France.|CNRS, UMR 8256, B2A, F-75005, Paris, France.
authors.forename: Hadi S
authors.initials: HS
authors.lastname: Zanjani
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, P.O. Box 21247, Baltimore, MD, 21228, USA. vogel.michael1066@gmail.com.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Vogel
authors.affiliation: Sorbonne Universités UPMC Univ. Paris 06, IBPS, UMR 8256, Biological Adaptation and Ageing, B2A, 75005, Paris, France.|CNRS, UMR 8256, B2A, F-75005, Paris, France.|Institut de la Longévité, APHP, DHU Fast, 94205, Ivry-Sur-Seine, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Mariani
mesh_terms: D000375:Aging / Q000378:metabolism / Q000473:pathology; D000704:Analysis of Variance; D000818:Animals; D064026:Calbindins / Q000378:metabolism; D002452:Cell Count; D016923:Cell Death / Q000502:physiology; D048429:Cell Size; D002470:Cell Survival / Q000502:physiology; D002531:Cerebellum / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D010784:Photomicrography; D017470:Receptors, Glutamate / Q000235:genetics / Q000378:metabolism*
chemical_list: D064026:Calbindins; D017470:Receptors, Glutamate; C107913:glutamate receptor delta 2
keywords: Cerebellum; Delta 2 glutamate receptor; Granule cells; Numerical matching