NMDA receptor-dependent metaplasticity by high-frequency magnetic stimulation.

Tursonjan Tokay,Volker Zschorlich,Timo Kirschstein,Rüdiger Köhling,Marco Rohde

doi:10.1155/2014/684238

Abstract

High-frequency magnetic stimulation (HFMS) can elicit N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP) at Schaffer collateral-CA1 pyramidal cell synapses. Here, we investigated the priming effect of HFMS on the subsequent magnitude of electrically induced LTP in the CA1 region of rat hippocampal slices using field excitatory postsynaptic potential (fEPSP) recordings. In control slices, electrical high-frequency conditioning stimulation (CS) could reliably induce LTP. In contrast, the same CS protocol resulted in long-term depression when HFMS was delivered to the slice 30 min prior to the electrical stimulation. HFMS-priming was diminished when applied in the presence of the metabotropic glutamate receptor antagonists (RS)-α-methylserine-O-phosphate (MSOP) and (RS)-α-methyl-4-carboxyphenylglycine (MCPG). Moreover, when HFMS was delivered in the presence of the NMDA receptor-antagonist D-2-amino-5-phosphonovalerate (50 µM), CS-induced electrical LTP was again as high as under control conditions in slices without priming. These results demonstrate that HFMS significantly reduced the propensity of subsequent electrical LTP and show that both metabotropic glutamate and NMDA receptor activation were involved in this form of HFMS-induced metaplasticity.

Highlights

High-frequency neuronal activity can induce persistent changes in synaptic strength resulting in a long-lasting increase of the postsynaptic response called long-term potentiation or LTP [1]
These results demonstrate that high-frequency magnetic stimulation (HFMS) significantly reduced the propensity of subsequent electrical LTP and show that both metabotropic glutamate and NMDA receptor activation were involved in this form of HFMS-induced metaplasticity
The paired-pulse ratio was significantly higher at 60 min after conditioning stimulation (CS) compared to baseline (114 ± 5% of baseline PPR, n = 11, P < 0.01 versus baseline, paired t-test) suggesting a presynaptic contribution to CS-induced long-term depression (LTD) in HFMS-primed slices

Summary

Introduction

High-frequency neuronal activity can induce persistent changes in synaptic strength resulting in a long-lasting increase of the postsynaptic response called long-term potentiation or LTP [1]. One major mechanism of LTP is the activation of postsynaptic NMDA receptors. It is currently accepted that electrical highfrequency stimulation of afferent fibers results in excessive glutamate release and subsequent AMPA receptor-mediated depolarization of the postsynaptic membrane which enables relief from the Mg2+ block [4]. NMDA receptor activation, in turn, leads to Ca2+ influx and activation of a number of metabolic processes resulting in a long-lasting enhancement of AMPA receptor-mediated responses. Weak stimulation or priming of afferent fibers that was insufficient to induce long-lasting changes by itself was able to significantly inhibit subsequent LTP induction, and this process—called metaplasticity—was NMDA receptordependent [5]. Metaplasticity is regarded as a form of homeostasis in which the history of previous neuronal activation influences the direction and degree of synaptic plasticity elicited by a given stimulus [6]

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