摘要

Recent studies have found that in the cerebellum, the delta 2 glutamate receptor (GluR delta 2) 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 GluR delta 2 knockout mice, the absence of GluR delta 2 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 GluR delta 2 expression in the hotfoot mutant (GluR delta 2 (ho/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 GluR delta 2 (ho/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 GluR delta 2 (ho/ho) mutants. The interpretation of the results is that the GluR delta 2 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.

  • 出版日期2016-12