Zinc enhances hippocampal long-term potentiation at CA1 synapses through NR2B containing NMDA receptors.

John A Sullivan,Patric K Stanton,Alexander A Moghadam,Linnea R Vose,Xiao-Lei Zhang,Arthur P Sullivan,Victor A Fried

doi:10.1371/journal.pone.0205907

John A Sullivan, Patric K Stanton + Show 5 more

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https://doi.org/10.1371/journal.pone.0205907

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Journal: PloS one	Publication Date: Nov 28, 2018
Citations: 11	License type: CC BY 4.0

Affiliation: New York Medical College, Touro College

Abstract

The role of zinc (Zn2+), a modulator of N-methyl-D-aspartate (NMDA) receptors, in regulating long-term synaptic plasticity at hippocampal CA1 synapses is poorly understood. The effects of exogenous application of Zn2+ and of chelation of endogenous Zn2+ were examined on long-term potentiation (LTP) of stimulus-evoked synaptic transmission at Schaffer collateral (SCH) synapses in field CA1 of mouse hippocampal slices using whole-cell patch clamp and field recordings. Low micromolar concentrations of exogenous Zn2+ enhanced the induction of LTP, and this effect required activation of NMDA receptors containing NR2B subunits. Zn2+ elicited a selective increase in NMDA/NR2B fEPSPs, and removal of endogenous Zn2+ with high-affinity Zn2+ chelators robustly reduced the magnitude of stimulus-evoked LTP. Taken together, our data show that Zn2+ at physiological concentrations enhances activation of NMDA receptors containing NR2B subunits, and that this effect enhances the magnitude of LTP.

Highlights

Plasticity at hippocampal synapses is influenced by a number of endogenous factors including Zn2+, which acts on N-methyl-D-aspartate glutamate receptors (NMDAR) involved in the induction of long-term potentiation (LTP)
To test the potential role of Zn2+ in regulating synaptic plasticity, we commenced by bath applying exogenous Zn2+ to mouse hippocampal slices at a concentration of 1μM to evaluate stimulus-evoked LTP at Schaffer collateral (SCH) synapses in field CA1
The data presented here support the conclusion that low micromolar zinc enhances TBSinduced LTP of SCH-CA1 synapses through phosphorylation of NR2B subunits of NMDA receptors

Summary

Introduction

Plasticity at hippocampal synapses is influenced by a number of endogenous factors including Zn2+, which acts on N-methyl-D-aspartate glutamate receptors (NMDAR) involved in the induction of long-term potentiation (LTP). Zn2+ is released from presynaptic vesicles by low frequency synaptic transmission and interacts with multiple receptors that are involved in the induction of LTP, including NMDAR [1,2,3,4]. Removal of vesicular Zn2+ via either genetic ablation of the ZnT3 Zn2+ synaptic vesicle transporter, or Zn2+ chelation with CaEDTA, have been reported to impair LTP, suggesting that endogenous synapticallyreleased Zn2+ may play a role in gating the induction of LTP [8,9]. Izumi and colleagues suggest that removal of Zn2+ using CaEDTA, a membrane impermeable metal chelator with high.

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