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Maturation of Purkinje cell firing properties relies on granule cell neurogenesis

View ORCID ProfileMeike E. van der Heijden, Elizabeth P. Lackey, Fatma S. Işleyen, Amanda M. Brown, Ross Perez, Tao Lin, View ORCID ProfileHuda Y. Zoghbi, View ORCID ProfileRoy V. Sillitoe
doi: https://doi.org/10.1101/2020.05.20.106732
Meike E. van der Heijden
1Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA
5Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, Texas, 77030, USA
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  • ORCID record for Meike E. van der Heijden
Elizabeth P. Lackey
1Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA
2Department of Neuroscience, Baylor College of Medicine, Houston, Texas, USA
5Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, Texas, 77030, USA
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Fatma S. Işleyen
1Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA
3Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, USA
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Amanda M. Brown
1Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA
2Department of Neuroscience, Baylor College of Medicine, Houston, Texas, USA
5Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, Texas, 77030, USA
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Ross Perez
5Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, Texas, 77030, USA
6University of St. Thomas, Houston, Texas, USA
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Tao Lin
1Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA
5Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, Texas, 77030, USA
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Huda Y. Zoghbi
2Department of Neuroscience, Baylor College of Medicine, Houston, Texas, USA
3Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, USA
5Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, Texas, 77030, USA
7Howard Hughes Medical Institute, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
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Roy V. Sillitoe
1Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA
2Department of Neuroscience, Baylor College of Medicine, Houston, Texas, USA
3Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, USA
4Development, Disease Models & Therapeutics Graduate Program, Baylor College of Medicine, Houston, Texas, USA
5Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, Texas, 77030, USA
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  • For correspondence: [email protected]
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SUMMARY

Preterm infants that suffer cerebellar insults often develop motor disorders and cognitive difficulty. Granule cells are especially vulnerable, and they likely instigate disease by impairing the function of Purkinje cells. Here, we use regional genetic manipulations and in vivo electrophysiology to test whether granule cells help establish the firing properties of Purkinje cells during postnatal mouse development. We generated mice that lack granule cell neurogenesis and tracked the structural and functional consequences on Purkinje cells in these agranular pups. We reveal that Purkinje cells fail to acquire their typical connectivity and morphology, and the formation of characteristic Purkinje cell firing patterns is delayed by one week. We also show that the agranular pups have impaired motor behaviors and vocal skills. These data argue that granule cell neurogenesis sets the maturation time window for Purkinje cell function and refines cerebellar-dependent behaviors.

Competing Interest Statement

The authors have declared no competing interest.

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Posted May 23, 2020.
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Maturation of Purkinje cell firing properties relies on granule cell neurogenesis
Meike E. van der Heijden, Elizabeth P. Lackey, Fatma S. Işleyen, Amanda M. Brown, Ross Perez, Tao Lin, Huda Y. Zoghbi, Roy V. Sillitoe
bioRxiv 2020.05.20.106732; doi: https://doi.org/10.1101/2020.05.20.106732
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Maturation of Purkinje cell firing properties relies on granule cell neurogenesis
Meike E. van der Heijden, Elizabeth P. Lackey, Fatma S. Işleyen, Amanda M. Brown, Ross Perez, Tao Lin, Huda Y. Zoghbi, Roy V. Sillitoe
bioRxiv 2020.05.20.106732; doi: https://doi.org/10.1101/2020.05.20.106732

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