Involvement of protein-tyrosine phosphatase PTPMEG in motor learning and cerebellar long-term depression.
Although protein-tyrosine phosphorylation is important for hippocampus-dependent learning, its role in cerebellum-dependent learning remains unclear. We previously found that PTPMEG, a cytoplasmic protein-tyrosine phosphatase expressed in Purkinje cells (PCs), bound to the carboxyl-terminus of the glutamate receptor delta2 via the postsynaptic density-95/discs-large/ZO-1 domain of PTPMEG. In the present study, we generated PTPMEG-knockout (KO) mice, and addressed whether PTPMEG is involved in cerebellar plasticity and cerebellum-dependent learning. The structure of the cerebellum in PTPMEG-KO mice appeared grossly normal. However, we found that PTPMEG-KO mice showed severe impairment in the accelerated rotarod test. These mice also exhibited impairment in rapid acquisition of the cerebellum-dependent delay eyeblink conditioning, in which conditioned stimulus (450-ms tone) and unconditioned stimulus (100-ms periorbital electrical shock) were co-terminated. Moreover, long-term depression at parallel fiber-PC synapses was significantly attenuated in these mice. Developmental elimination of surplus climbing fibers and the physiological properties of excitatory synaptic inputs to PCs appeared normal in PTPMEG-KO mice. These results suggest that tyrosine dephosphorylation events regulated by PTPMEG are important for both motor learning and cerebellar synaptic plasticity.
Kina
Shin-ichiro
S
Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Tokyo, 108-8639, Japan.
Tezuka
Tohru
T
Kusakawa
Shinji
S
Kishimoto
Yasushi
Y
Kakizawa
Sho
S
Hashimoto
Koichi
K
Ohsugi
Miho
M
Kiyama
Yuji
Y
Horai
Reiko
R
Sudo
Katsuko
K
Kakuta
Shigeru
S
Iwakura
Yoichiro
Y
Iino
Masamitsu
M
Kano
Masanobu
M
Manabe
Toshiya
T
Yamamoto
Tadashi
T
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001767:Blinking / Q000502:physiology; D002531:Cerebellum / Q000166:cytology / Q000502:physiology*; D003213:Conditioning, Psychological / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression / Q000235:genetics / Q000502:physiology*; D008569:Memory Disorders / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000502:physiology / Q000528:radiation effects; D017027:Protein Tyrosine Phosphatases / Q000172:deficiency / Q000502:physiology*; D011597:Psychomotor Performance; D045442:Rotarod Performance Test / Q000379:methods; D013997:Time Factors
D017027:Protein Tyrosine Phosphatases