Genetic perturbation of postsynaptic activity regulates synapse elimination in developing cerebellum

Erika Lorenzetto, Luana Caselli, Guoping Feng, Weilong Yuan, Jeanne M. Nerbonne, Joshua R. Sanes, Mario Buffelli

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

In many parts of the vertebrate nervous system, synaptic connections are remodeled during early postnatal life. Neural activity plays an important role in regulating one such rearrangement, synapse elimination, in the developing neuromuscular system, but there is little direct evidence on roles of pre- or postsynaptic activity in regulating synapse elimination in the developing brain. To address this issue, we expressed a chloride channel-yellow fluorescent protein fusion in cerebellar Purkinje cells (PCs) of transgenic mice to decrease their excitability.Wethen assessed elimination of supernumerary climbing fiber inputs to PCs. Individual PCs are innervated by multiple climbing fibers at birth; all but one are eliminated during the first three postnatal weeks in wild-type mice, but multiple innervation persists for at least three months in the transgenic mice. The normal redistribution of climbing fiber synapses from PC somata to proximal dendrites was also blunted in transgenics. These results show that normal electrical activity of the postsynaptic cell is required for it to attain a mature innervation pattern.

Original languageEnglish
Pages (from-to)16475-16480
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number38
DOIs
StatePublished - Sep 22 2009

Keywords

  • Chloride channel
  • Climbing fiber
  • Purkinje cell

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