Age-dependent modulation of LTP by PTPζ

Abstract

Synaptic plasticity is regulated in part by the complex modulations of the intracellular phosphorylation state. Protein tyrosine phosphataseζ(PTPζ) is a receptor-like tyrosine phosphatase expressed primarily in the brain. The extracellular domain of PTPζ binds various cell-recognition, cell-adhesion molecules and growth factors. However, little is known about the functional roles of PTPζ. To investigate the role of PTPζ in synaptic transmission and plasticity, we recorded excitatory synaptic responses in the CA1 region of hippocampal slices obtained from PTPζ-deficient mice. Although we found no difference in basic synaptic properties such as paired-pulse facilitation between the genotypes, long-term potentiation (LTP) in mutant mice was age-dependently enhanced. Since properties of the NMDA receptor-mediated synaptic response before and during tetanic stimulation were indistinguishable between the genotypes, enhanced LTP in mutant mice was unlikely due to NMDA receptor modification by the lack of PTPζ. However, because LTP enhancement in mutant mice was dependent on NMDA receptor activation, we examined possible involvement of the process downstream of NMDA receptor activation. We conclude that PTPζ regulates synaptic plasticity through modification of intracellular biochemical processes involved in LTP expression via the control of tyrosine phosphorylation. [Jpn J Physiol 54 Suppl:S153 (2004)]