Hydrogen peroxide modulation of synaptic plasticity

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 H(2)O(2) reduces EPSPs in both potentiated and nonpotentiated synapses. Exposure of the slices to 20 microm H(2)O(2) did not affect expression of preestablished long-term potentiation (LTP) but prevented induction of new LTP and enhanced long-term depression (LTD). Surprisingly, 1 microm H(2)O(2) caused a twofold increase in LTP compared with controls, and it further enhanced NMDA-independent LTP. A low concentration of H(2)O(2) also suppressed LTD. Nifedipine, an L-type calcium channel blocker, did not affect control LTP but blocked effects of both 1 and 20 microm H(2)O(2). Calcineurin inhibitors [FK506 (FR900506) and cyclosporin A but not rapamycin] acted similarly and also restored LTP in the presence of 20 microm H(2)O(2). These results suggest that H(2)O(2) alters NMDA-independent, voltage-gated calcium channel-mediated LTP by activating calcineurin.