The Cerebellum

, Volume 17, Issue 1, pp 56–61 | Cite as

Climbing Fiber Development Is Impaired in Postnatal Car8 wdl Mice

Original Paper

Abstract

The cerebellum is critical for an array of motor functions. During postnatal development, the Purkinje cells (PCs) guide afferent topography to establish the final circuit. Perturbing PC morphogenesis or activity during development can result in climbing fiber (CF) multi-innervation or mis-patterning. Structural defects during circuit formation typically have long-term effects on behavior as they contribute to the phenotype of movement disorders such as cerebellar ataxia. The Car8 wdl mouse is one model in which early circuit destruction influences movement. However, although the loss of Car8 leads to the mis-wiring of afferent maps and abnormal PC firing, adult PC morphology is largely intact and there is no neurodegeneration. Here, we sought to uncover how defects in afferent connectivity arise in Car8 wdl mutants to resolve how functional deficits persist in motor diseases with subtle neuropathology. To address this problem, we analyzed CF development during the first 3 weeks of life. By immunolabeling CF terminals with VGLUT2, we found evidence of premature CF synapse elimination and delayed translocation from PC somata at postnatal day (P) 10 in Car8 wdl mice. Surprisingly, by P15, the wiring normalized, suggesting that CAR8 regulates the early but not the late stages of CF development. The data support the hypothesis of a defined sequence of events for cerebellar circuits to establish function.

Keywords

Cerebellum Development Climbing fiber Circuitry CAR8 Ataxia 

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Department of Pathology and Immunology, Baylor College of MedicineJan and Dan Duncan Neurological Research Institute of Texas Children’s HospitalHoustonUSA
  2. 2.Program in Developmental Biology, Baylor College of MedicineJan and Dan Duncan Neurological Research Institute of Texas Children’s HospitalHoustonUSA
  3. 3.Department of Neuroscience, Baylor College of MedicineJan and Dan Duncan Neurological Research Institute of Texas Children’s HospitalHoustonUSA

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