THE NMDA RECEPTOR REDOX SITE CONTROLS NMD A-RECEPTOR-MEDIATED LONG-TERM POTENTIATION

In order to evaluate the role of the NMDA receptor redox site in long- term potentiation (LTP), we have investigated the effects of two redox reagents, 5,5'-dithiobis-2-nitrobenzoic acid (DTNB) and tris(carboxye thyl)phosphine (TCEP) on the induction and expression of various forms of LTP. DTNB a thiol-oxidizing agent, irreversibly reduces by 50% NMD A receptor EPSP. In the presence of DTNB, the induction of tetanic and anoxic LTP are prevented. When tetanic or anoxic LTP were generated f irst, DTNB completely reverses the potentiation and TCEP a disulfide-r educing agent restores LTP to its initial level. These redox agents ha ve no effect on AMPA synaptic transmission and did not significantly m odify the induction and the expression of tetanic AMPA-LTP. These resu lts suggest that thiol-oxidizing compounds might be useful for the tre atment of cerebral ischemia.