Details

Autor(en) / Beteiligte

• 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

Titel

Involvement of protein-tyrosine phosphatase PTPMEG in motor learning and cerebellar long-term depression

Ist Teil von

• The European journal of neuroscience, 2007-10, Vol.26 (8), p.2269-2278

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

2007

Quelle

Psychology and Behavioral Sciences Collection

Beschreibungen/Notizen

• 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.