Enhancement of both long-term depression induction and optokinetic response adaptation in mice lacking delphilin.
In the cerebellum, Delphilin is expressed selectively in Purkinje cells (PCs) and is localized exclusively at parallel fiber (PF) synapses, where it interacts with glutamate receptor (GluR) delta2 that is essential for long-term depression (LTD), motor learning and cerebellar wiring. Delphilin ablation exerted little effect on the synaptic localization of GluRdelta2. There were no detectable abnormalities in cerebellar histology, PC cytology and PC synapse formation in contrast to GluRdelta2 mutant mice. However, LTD induction was facilitated at PF-PC synapses in Delphilin mutant mice. Intracellular Ca(2+) required for the induction of LTD appeared to be reduced in the mutant mice, while Ca(2+) influx through voltage-gated Ca(2+) channels and metabotropic GluR1-mediated slow synaptic response were similar between wild-type and mutant mice. We further showed that the gain-increase adaptation of the optokinetic response (OKR) was enhanced in the mutant mice. These findings are compatible with the idea that LTD induction at PF-PC synapses is a crucial rate-limiting step in OKR gain-increase adaptation, a simple form of motor learning. As exemplified in this study, enhancing synaptic plasticity at a specific synaptic site of a neural network is a useful approach to understanding the roles of multiple plasticity mechanisms at various cerebellar synapses in motor control and learning.
Department of Molecular Neurobiology and Pharmacology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Tomonori
T
Takeuchi
Gen
G
Ohtsuki
Takashi
T
Yoshida
Masahiro
M
Fukaya
Tasuku
T
Wainai
Manami
M
Yamashita
Yoshito
Y
Yamazaki
Hisashi
H
Mori
Kenji
K
Sakimura
Susumu
S
Kawamoto
Masahiko
M
Watanabe
Tomoo
T
Hirano
Masayoshi
M
Mishina
D000222:Adaptation, Physiological / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002531:Cerebellum / Q000033:anatomy & histology; D017931:DNA Primers; D019706:Excitatory Postsynaptic Potentials; D005133:Eye Movements; D036881:Long-Term Synaptic Depression / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D018091:Receptors, AMPA / Q000378:metabolism
D017931:DNA Primers; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; C447759:delphilin; C104722:glutamate receptor ionotropic, AMPA 2