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

First Author  Kina S Year  2007
Journal  Eur J Neurosci Volume  26
Issue  8 Pages  2269-78
PubMed ID  17953619 Mgi Jnum  J:127245
Mgi Id  MGI:3763469 Doi  10.1111/j.1460-9568.2007.05829.x
Citation  Kina S, et al. (2007) Involvement of protein-tyrosine phosphatase PTPMEG in motor learning and cerebellar long-term depression. Eur J Neurosci 26(8):2269-78
abstractText  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.
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