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 g...

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Published in:The European journal of neuroscience 2007-10, Vol.26 (8), p.2269-2278
Main Authors: Kina, Shin-ichiro, Tezuka, Tohru, Kusakawa, Shinji, Kishimoto, Yasushi, Kakizawa, Sho, Hashimoto, Koichi, Ohsugi, Miho, Kiyama, Yuji, Horai, Reiko, Sudo, Katsuko, Kakuta, Shigeru, Iwakura, Yoichiro, Iino, Masamitsu, Kano, Masanobu, Manabe, Toshiya, Yamamoto, Tadashi
Format: Article
Language:English
Subjects:
Animals
Behavior, Animal - physiology
Blinking - physiology
cerebellum
Cerebellum - cytology
Cerebellum - physiology
Conditioning (Psychology) - physiology
Dose-Response Relationship, Drug
Electric Stimulation - methods
eyeblink conditioning
In Vitro Techniques
knockout mice
Long-Term Synaptic Depression - genetics
Long-Term Synaptic Depression - physiology
Memory Disorders - genetics
Mice
Mice, Inbred C57BL
Mice, Knockout
Motor Activity - genetics
Motor Activity - physiology
Neurons - physiology
Neurons - radiation effects
phosphorylation
Protein Tyrosine Phosphatases - deficiency
Protein Tyrosine Phosphatases - physiology
Psychomotor Performance
Purkinje cells
Rotarod Performance Test - methods
Time Factors
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Summary: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 δ2 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.
ISSN:0953-816X
1460-9568
DOI:10.1111/j.1460-9568.2007.05829.x