Genetic perturbation of postsynaptic activity regulates synapse elimination in developing cerebellum
- 22 September 2009
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 106 (38), 16475-16480
- https://doi.org/10.1073/pnas.0907298106
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. We then 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.Keywords
This publication has 47 references indexed in Scilit:
- Signaling Mechanisms Linking Neuronal Activity to Gene Expression and Plasticity of the Nervous SystemAnnual Review of Neuroscience, 2008
- TrkB is necessary for pruning at the climbing fibre–Purkinje cell synapse in the developing murine cerebellumThe Journal of Physiology, 2007
- Requirement of TrkB for synapse elimination in developing cerebellar Purkinje cellsBrain Cell Biology, 2007
- mGluR1 in Cerebellar Purkinje Cells Essential for Long-Term Depression, Synapse Elimination, and Motor CoordinationScience, 2000
- DEVELOPMENT OF THE VERTEBRATE NEUROMUSCULAR JUNCTIONAnnual Review of Neuroscience, 1999
- Cre–mediated chromosome loss in miceNature Genetics, 1997
- Persistent Multiple Climbing Fiber Innervationof Cerebellar Purkinje Cellsin Mice Lacking mGluR1Neuron, 1997
- Regression of functional synapses in the immature mammalian cerebellumTrends in Neurosciences, 1982
- Multiple innervation of cerebellar Purkinje cells by climbing fibres in staggerer mutant mouseNature, 1980
- Multiple innervation of purkinje cells by climbing fibers in the cerebellum of the weaver mutant mouseJournal of Neurobiology, 1976