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

Kazue Niisato; Akihiro Fujikawa; Shoji Komai; Takafumi Shintani; Eiji Watanabe; Gaku Sakaguchi; Goro Katsuura; Toshiya Manabe; Masaharu Noda

doi:10.1523/JNEUROSCI.2565.04.2005

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

J Neurosci. 2005 Feb 2;25(5):1081-8. doi: 10.1523/JNEUROSCI.2565.04.2005.

Authors

Kazue Niisato¹, Akihiro Fujikawa, Shoji Komai, Takafumi Shintani, Eiji Watanabe, Gaku Sakaguchi, Goro Katsuura, Toshiya Manabe, Masaharu Noda

Affiliation

¹ Division of Neuronal Network, Department of Basic Medical Sciences, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aging / metabolism
Aging / psychology*
Amides / pharmacology
Animals
Chondroitin Sulfate Proteoglycans
Enzyme Activation / drug effects
Excitatory Postsynaptic Potentials / drug effects
Excitatory Postsynaptic Potentials / physiology*
Hippocampus / enzymology*
Hippocampus / physiology
Intracellular Signaling Peptides and Proteins
Long-Term Potentiation / physiology*
Male
Maze Learning / physiology*
Memory Disorders / enzymology*
Memory Disorders / genetics
Mice
Mice, Inbred C57BL
Mice, Knockout
Nerve Tissue Proteins / deficiency
Nerve Tissue Proteins / genetics
Nerve Tissue Proteins / physiology*
Phenotype
Protein Serine-Threonine Kinases / physiology*
Protein Tyrosine Phosphatases / deficiency
Protein Tyrosine Phosphatases / genetics
Protein Tyrosine Phosphatases / physiology*
Pyridines / pharmacology
Receptor-Like Protein Tyrosine Phosphatases, Class 5
Receptors, Cell Surface / deficiency
Receptors, Cell Surface / genetics
Receptors, Cell Surface / physiology*
Signal Transduction / drug effects
Signal Transduction / physiology
rho-Associated Kinases

Substances

Amides
Chondroitin Sulfate Proteoglycans
Intracellular Signaling Peptides and Proteins
Nerve Tissue Proteins
Pyridines
Receptors, Cell Surface
Y 27632
Protein Serine-Threonine Kinases
rho-Associated Kinases
Protein Tyrosine Phosphatases
Ptprz1 protein, mouse
Receptor-Like Protein Tyrosine Phosphatases, Class 5