PLPP/CIN regulates bidirectional synaptic plasticity via GluN2A interaction with postsynaptic proteins.

Ji-Eun Kim,Yeon-Joo Kim,Min Ju Kim,Hye-Won Hyun,Duk-Shin Lee,Ji Yang Kim,Ah-Reum Ko,Tae-Cheon Kang

doi:10.1038/srep26576

Abstract

Dendritic spines are dynamic structures whose efficacies and morphologies are modulated by activity-dependent synaptic plasticity. The actin cytoskeleton plays an important role in stabilization and structural modification of spines. However, the regulatory mechanism by which it alters the plasticity threshold remains elusive. Here, we demonstrate the role of pyridoxal-5′-phosphate phosphatase/chronophin (PLPP/CIN), one of the cofilin-mediated F-actin regulators, in modulating synaptic plasticity in vivo. PLPP/CIN transgenic (Tg) mice had immature spines with small heads, while PLPP/CIN knockout (KO) mice had gigantic spines. Furthermore, PLPP/CIN Tg mice exhibited enhanced synaptic plasticity, but KO mice showed abnormal synaptic plasticity. The PLPP/CIN-induced alterations in synaptic plasticity were consistent with the acquisition and the recall capacity of spatial learning. PLPP/CIN also enhanced N-methyl-D-aspartate receptor (GluN) functionality by regulating the coupling of GluN2A with interacting proteins, particularly postsynaptic density-95 (PSD95). Therefore, these results suggest that PLPP/CIN may be an important factor for regulating the plasticity threshold.

Highlights

Long-term potentiation (LTP) and its counterpart, long-term depression (LTD), represent synaptic plasticity, which involves learning, memory and experience-dependent development of cortical circuitry[1]
Co-immunoprecipitation with GluN subunit 2A (GluN2A) showed that PLPP/CIN could not alter the binding of GluN2A with GluN1 or GluN2B. These findings indicate that PLPP/ CIN may not affect the dynamics of GluN distribution and the heterotrimerization
PLPP/CIN overexpression or deletion did not change GABAergic neurotransmission and a short-term presynaptic plasticity. These findings indicate that PLPP/CIN may not affect basal neurotransmission, and spine morphology may not represent the synaptic strength under basal condition

Summary

Introduction

Long-term potentiation (LTP) and its counterpart, long-term depression (LTD), represent synaptic plasticity, which involves learning, memory and experience-dependent development of cortical circuitry[1]. LTD is an activity-dependent reduction in the efficacy of neuronal synapses through F-actin destabilization and GluA internalization, which is mediated by phosphatases including calcineurin (CN)[4]. Both LTP and LTD are initiated by the entry of Ca2+ via excitatory receptors including N-methyl-D-aspartate receptor (GluN)[5]. Some research has shown that abnormal actin dynamics inhibit LTP and LTD inductions[4,16] It remains to be determined whether F-actin changes the threshold of synaptic plasticity and the molecular mechanisms involved. PLPP/CIN is a potentially important factor for regulating the plasticity threshold via F-actin-mediated GluN activity

Methods

Results

Conclusion