In CA1 hippocampal neurons, the redox state of NMDA receptors determines LTP expressed by NMDA but not by AMPA receptors.

1. Using extracellular recording techniques in the CA1 region of the rat hippocampus, we have evaluated the effects of the redox reagents 5,5O-dithiobis-2-nitrobenzoic acid (DTNB) and tris (carboxyethyl) phosphine (TCEP) on long-term potentiation (LTP) expressed by alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors. In physiological conditions a high-frequency stimulation (HFS) of Schaffer collateral-commissural fibers induced a LTP expressed by a persistent increase (73 +/- 13%, mean +/- SE, n = 8/10) of AMPA field potentials (LTPA). In the presence of 10 microM of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and reduced concentration of Mg2+ (0.1 mM) to boost NMDA receptors, the HFS induced LTP of NMDA field potentials (LTPN; 62 +/- 11%, n = 8/10). 2. The thiol-oxidizing reagent DTNB (200 microM) reduced, by 46 +/- 5% (n = 24), NMDA-receptor field potentials (NMDA-FP), and this effect could not be reversed by extensive washing. The disulfide-reducing agent TCEP (200 microM) slightly increased AMPA-FP and reversed the DTNB-induced inhibition of NMDA-FP. 3. DTNB (200 microM, 10 min), and TCEP (200 microM, 20 min), had no effect on AMPA-FP (98 +/- 3% and 101 +/- 5%, respectively, n = 12). 4. DTNB (200 microM, 15 min) did not prevent the induction or expression of LTPA (-12 and -5%, respectively, n = 8/8). Similar results were observed with TCEP (200 microM, 20 min).(ABSTRACT TRUNCATED AT 250 WORDS)