Genetic perturbation of postsynaptic activity regulates synapse elimination in developing cerebellum.
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.
Lorenzetto
Erika
E
National Institute of Neuroscience and Department of Neurological and Visual Sciences, Section of Physiology, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy.
Caselli
Luana
L
Feng
Guoping
G
Yuan
Weilong
W
Nerbonne
Jeanne M
JM
Sanes
Joshua R
JR
Buffelli
Mario
M
D000818:Animals; D002460:Cell Line; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development / Q000502:physiology*; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009043:Motor Activity / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D011689:Purkinje Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017783:Superior Cervical Ganglion / Q000166:cytology; D013569:Synapses / Q000502:physiology*; D014162:Transfection
C086321:CLC-1 channel; D018118:Chloride Channels; D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins