LONG-TERM DEPRESSION OF NAIVE SYNAPSES IN ADULT HIPPOCAMPUS INDUCED BY ASYNCHRONOUS SYNAPTIC ACTIVITY

1. Two independent Schaffer collateral pathways converging to the same pyramidal cell were alternately stimulated by 2-Hz trains (900 pulses ) offset by a 150-ms interval in adult rat hippocampal slices. The sec ond input underwent an immediate and persistent long-term depression ( LTD). Depression in the first input was smaller than the second input. A narrower interpulse interval (20 ms) failed to induce LTD in either input. 2. Neither the N-methyl-D-aspartate receptor antagonist DL-2-a mino-5-phosphonovaleric acid nor the metabotropic glutamate receptor a ntagonist (+)-alpha-methyl-4-carboxylphenyl-glycine blocked this assoc iative LTD. However, coapplication of these two antagonists blocked LT D. 3. Associative LTD was blocked by prior injection of the Ca2+ chela tor bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid into the postsynap tic cell and by bath-applied L-N-G-nitroarginine, a nitric oxide synth esis inhibitor. 4. We propose that temporally confined, asynchronous s ynaptic activity weakens the efficacy of naive synapses in slices from the adult hippocampus.