Maturation of Purkinje cell firing properties relies on neurogenesis of excitatory neurons

eLife

Meike E van der Heijden¹  Tao Lin¹  Amanda M Brown²  Sarah G Donofrio²  Elizabeth P Lackey²  Roy V Sillitoe³  Fatma S Ișleyen⁴  Ross Perez⁵  Huda Y Zoghbi⁶ 

[1] Department of Pathology and Immunology, Baylor College of Medicine, Houston, United States;Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, United States;Department of Pathology and Immunology, Baylor College of Medicine, Houston, United States;Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, United States;Department of Neuroscience, Baylor College of Medicine, Houston, United States;Department of Pathology and Immunology, Baylor College of Medicine, Houston, United States;Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, United States;Department of Neuroscience, Baylor College of Medicine, Houston, United States;Program in Developmental Biology, Baylor College of Medicine, Houston, United States;Development, Disease Models and Therapeutics Graduate Program, Baylor College of Medicine, Houston, United States;Department of Pathology and Immunology, Baylor College of Medicine, Houston, United States;Program in Developmental Biology, Baylor College of Medicine, Houston, United States;Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, United States;Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, United States;Department of Neuroscience, Baylor College of Medicine, Houston, United States;Program in Developmental Biology, Baylor College of Medicine, Houston, United States;Howard Hughes Medical Institute, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States;

关键词: Purkinje cells;    granule cells;    cerebellum;    electrophysiology;    development;    behavior;    Mouse;   

DOI  :  10.7554/eLife.68045

来源: eLife Sciences Publications, Ltd

【 摘 要 】

Preterm infants that suffer cerebellar insults often develop motor disorders and cognitive difficulty. Excitatory granule cells, the most numerous neuron type in the brain, are especially vulnerable and likely instigate disease by impairing the function of their targets, the Purkinje cells. Here, we use regional genetic manipulations and in vivo electrophysiology to test whether excitatory neurons establish the firing properties of Purkinje cells during postnatal mouse development. We generated mutant mice that lack the majority of excitatory cerebellar neurons and tracked the structural and functional consequences on Purkinje cells. We reveal that Purkinje cells fail to acquire their typical morphology and connectivity, and that the concomitant transformation of Purkinje cell firing activity does not occur either. We also show that our mutant pups have impaired motor behaviors and vocal skills. These data argue that excitatory cerebellar neurons define the maturation time-window for postnatal Purkinje cell functions and refine cerebellar-dependent behaviors.

【 授权许可】

CC BY