A ROLE FOR SUPEROXIDE IN PROTEIN-KINASE-C ACTIVATION AND INDUCTION OFLONG-TERM POTENTIATION

The induction of several forms of long-term potentiation (LTP) of syna ptic transmission in the CA1 region of the mammalian hippocampus is de pendent on N-methyl-D-aspartate receptor activation and the subsequent activation of protein kinase C (PKC), but the mechanisms that underli e the regulation of PKC in this context are largely unknown. It is kno wn that reactive oxygen species, including superoxide, are produced by N-methyl-D-aspartate receptor activation in neurons, and recent studi es have suggested that some reactive oxygen species can modulate PKC i n vitro. Thus, we have investigated the role of superoxide in both the induction of LTP and the activation of PKC during LTP. We found that incubation of hippocampal slices with superoxide scavengers inhibited the induction of LTP. The effects of superoxide on LTP induction may i nvolve PKC, as we observed that superoxide was required for appropriat e modulation of PKC activation during the induction of LTP. In this re spect, superoxide appears to work in conjunction with nitric oxide, wh ich was required for a portion of the LTP-associated changes in PKC ac tivity as well. Our observations indicate that superoxide and nitric o xide together regulate PKC in a physiologic context and that this type of regulation occurs during the induction of LTP in the hippocampus.