Roles of glutamate receptor delta 2 subunit (GluRdelta 2) and metabotropic glutamate receptor subtype 1 (mGluR1) in climbing fiber synapse elimination during postnatal cerebellar development.
Climbing fiber (CF) synapse formation onto cerebellar Purkinje cells (PCs) is critically dependent on the synaptogenesis from parallel fibers (PFs), the other input to PCs. Previous studies revealed that deletion of the glutamate receptor delta2 subunit (GluRdelta2) gene results in persistent multiple CF innervation of PCs with impaired PF synaptogenesis, whereas mutation of the metabotropic glutamate receptor subtype 1 (mGluR1) gene causes multiple CF innervation with normal PF synaptogenesis. We demonstrate that atypical CF-mediated EPSCs (CF-EPSCs) with slow rise times and small amplitudes coexisted with typical CF-EPSCs with fast rise times and large amplitudes in PCs from GluRdelta2 mutant cerebellar slices. CF-EPSCs in mGluR1 mutant and wild-type PCs had fast rise times. Atypical slow CF responses of GluRdelta2 mutant PCs were associated with voltage-dependent Ca(2+) signals that were confined to PC distal dendrites. In the wild-type and mGluR1 mutant PCs, CF-induced Ca(2+) signals involved both proximal and distal dendrites. Morphologically, CFs of GluRdelta2 mutant mice extended to the superficial regions of the molecular layer, whereas those of wild-type and mGluR1 mutant mice did not innervate the superficial one-fifth of the molecular layer. It is therefore likely that surplus CFs of GluRdelta2 mutant mice form ectopic synapses onto distal dendrites, whereas those of wild-type and mGluR1 mutant mice innervate proximal dendrites. These findings suggest that GluRdelta2 is required for consolidating PF synapses and restricting CF synapses to the proximal dendrites, whereas the mGluR1-signaling pathway does not affect PF synaptogenesis but is involved in eliminating surplus CF synapses at the proximal dendrites.
Hashimoto
K
K
Department of Physiology, Kanazawa University School of Medicine, Takara-machi, Kanazawa 920-8640, Japan.
Ichikawa
R
R
Takechi
H
H
Inoue
Y
Y
Aiba
A
A
Sakimura
K
K
Mishina
M
M
Hashikawa
T
T
Konnerth
A
A
Watanabe
M
M
Kano
M
M
D000375:Aging / Q000378:metabolism; D000818:Animals; D020013:Calcium Signaling / Q000502:physiology; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D003433:Crosses, Genetic; D003712:Dendrites / Q000502:physiology / Q000648:ultrastructure; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D066298:In Vitro Techniques; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D009154:Mutation; D009412:Nerve Fibers / Q000502:physiology*; D009847:Olivary Nucleus / Q000502:physiology; D018408:Patch-Clamp Techniques; D011689:Purkinje Cells / Q000166:cytology / Q000502:physiology; D011930:Reaction Time / Q000502:physiology; D017470:Receptors, Glutamate / Q000235:genetics / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000378:metabolism*
D017470:Receptors, Glutamate; D018094:Receptors, Metabotropic Glutamate; C107913:glutamate receptor delta 2; C104077:metabotropic glutamate receptor type 1