The complementary nature of long-term depression and potentiation revealed by dual component excitatory postsynaptic...

Homosynaptic long-term depression and long-term potentiation were studied in hippocampal slices from 12-18-day-old rats using field excitatory postsynaptic potentials recorded in the CA1 subfield (stratum radiatum). Independent estimates of the alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA) and the N-methyl-D-aspartate receptor-mediated components of the field excitatory postsynaptic potential were obtained in parallel using early and late measurements of a dual component excitatory postsynaptic potential in a solution containing low (0.1 mM) magnesium and 1 microM of the AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Long-term depression, induced by 2 Hz stimulation for 10 min, was observed as an equal relative depression of the AMPA and N-methyl-D-aspartate receptor-mediated components of the field excitatory postsynaptic potential, whereas long-term potentiation induced by single or repeated high-frequency stimulation, was seen initially as a predominant potentiation of the AMPA receptor-mediated component. Within the first 30-60 min, long-term potentiation gradually changed to more equal increases of the two components of the excitatory postsynaptic potential. During alternating induction of long-term depression and long-term potentiation, the AMPA and N-methyl-D-aspartate receptor-mediated components could both be repeatedly regulated up and down. Long-term depression and long-term potentiation also showed several signs of interaction with each other during such experiments; e.g., long-term depression removed the occlusive effect of large long-term potentiation on a subsequent long-term potentiation, and long-term potentiation applied after the induction of long-term depression was found to be more stable than otherwise. The results support the notion that long-term depression and long-term potentiation employ changes in a common synaptic property. A tentative mechanism for this modification, expressed as equal changes of AMPA and N-methyl-D-aspartate receptor-mediated components of the excitatory postsynaptic potential, is an alteration in transmitter release, while the initial asymmetric part of long-term potentiation indicates involvement of an additional short-term modification.