RT Journal Article SR Electronic T1 Age-Dependent Enhancement of Hippocampal Long-Term Potentiation and Impairment of Spatial Learning through the Rho-Associated Kinase Pathway in Protein Tyrosine Phosphatase Receptor Type Z-Deficient Mice JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 1081 OP 1088 DO 10.1523/JNEUROSCI.2565.04.2005 VO 25 IS 5 A1 Kazue Niisato A1 Akihiro Fujikawa A1 Shoji Komai A1 Takafumi Shintani A1 Eiji Watanabe A1 Gaku Sakaguchi A1 Goro Katsuura A1 Toshiya Manabe A1 Masaharu Noda YR 2005 UL http://www.jneurosci.org/content/25/5/1081.abstract AB Although protein tyrosine phosphatases (PTPs) are expressed abundantly in the brain, their roles in synaptic plasticity have not been well elucidated. In this study, we have examined the physiological functions of Ptprz, which is a receptor-type PTP expressed predominantly in the brain as a chondroitin sulfate proteoglycan. We have examined phenotypes of mutant mice deficient in Ptprz using electrophysiological, pharmacological, and behavioral approaches. Mutant mice exhibit enhanced long-term potentiation (LTP) in the CA1 region of hippocampal slices and impaired spatial learning abilities in an age-dependent manner: young adult (<10 weeks old) mutant mice show normal LTP and learning abilities in the Morris water maze task, whereas adult (>13 weeks old) mutant mice exhibit enhanced LTP and impairment in the task. The enhanced LTP is specifically canceled out by pharmacological inhibition of Rho-associated kinase (ROCK), a major downstream effector of Rho. These findings suggest that the lack of Ptprz leads to aberrant activation of ROCK and resultantly to enhanced LTP in the slice and learning impairments in the animal.