Hydrogen peroxide modulation of synaptic plasticity

Abstract

Unlike the proposed role of reactive oxygen species in neurodegeneration, acute effects of reactive oxygen on synaptic plasticity are poorly understood. Using rat hippocampal slices, we found that exposure to a high concentration (0.5-5 mM) of H2O2 reduces EPSPs in both potentiated and nonpotentiated synapses. Exposure of the slices to 20 μM H2O2 did not affect expression of preestablished long-term potentiation (LTP) but prevented induction of new LTP and enhanced long-term depression (LTD). Surprisingly, 1 μM H2O2 caused a twofold increase in LTP compared with controls, and it further enhanced NMDA-independent LTP. A low concentration of H2O2 also suppressed LTD. Nifedipine, an L-type calcium channel blocker, did not affect control LTP but blocked effects of both 1 and 20 μM H2O2. Calcineurin inhibitors [FK506 (FR900506) and cyclosporin A but not rapamycin] acted similarly and also restored LTP in the presence of 20 μM H2O2. These results suggest that H2O2 alters NMDA-independent, voltage-gated calcium channel-mediated LTP by activating calcineurin.