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

Overview

Journal J Neurosci

Specialty Neurology

Date 2005 Feb 4

PMID 15689543

Citations 27

Authors

Kazue Niisato

Akihiro Fujikawa

Shoji Komai

Takafumi Shintani

Eiji Watanabe

Gaku Sakaguchi

Goro Katsuura

Toshiya Manabe

Masaharu Noda

Affiliations

Soon will be listed here.

Abstract

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.

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