V39. Repetitive magnetic stimulation (rMS) leads to NMDA receptor-dependent metaplasticity in hippocampal slices in vitro

Abstract

Long-term potentiation (LTP) is widely accepted as a major mechanism of information storage in the brain. Experimentally, LTP is induced by electrical stimulation of afferent fibers using various high-frequency stimulation paradigms. We have previously shown that repetitive magnetic stimulation (rMS) can also elicit LTP at Schaffer collateral-CA1 pyramidal cell synapses, which was N-methyl- d -aspartate (NMDA) receptor-dependent. In the current study, we investigated the priming effect of rMS on the subsequent magnitude of electrically induced LTP in the CA1 region of rat hippocampal slices. To this end, we first stimulated the afferent fibers using rMS, and then started the recording of field excitatory postsynaptic potentials (fEPSPs). Electrical stimulation (ES) was administered at 30 min after rMS in order to induce LTP. Under control conditions, ES could reliably induce LTP in naive slices. In contrast, the same ES protocol resulted in long-term depression when rMS was delivered to the slice 30 min prior to ES. Thus, rMS-priming prevented subsequent ES-induced LTP. The effect of rMS-priming was significantly 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). In order to study the effects of rMS on CA1 hippocampal synapses directly,we conducted another set of experiments starting the fEPSP recording before rMS. In this case, rMS itself led to a significant enhancement of the fEPSP which was then reduced to baseline level by decreasing the stimulation strength before ES was administered. Under these conditions, ES did increase the fEPSP, but the magnitude of LTP in rMS-primed slices was significantly lower than the LTP obtained in unprimed slices. Moreover, when rMS was delivered in the presence of the NMDA receptor-antagonist D-2-amino-5-phosphonovalerate (50 μM) which itself completely blocked the rMS-induced fEPSP enhancement, ES-induced LTP was again as high as under control conditions in slices without priming. These results demonstrate that rMS-priming significantly reduced the propensity of subsequent electrical LTP, and show that both metabotropic glutamate and NMDA receptor activation were involved in this form of rMS-induced metaplasticity.