Homosynaptic Long-Term Depression in Area CA1 of Hippocampus and Effects of N-Methyl-D-Aspartate Receptor Blockade

摘要

We tested a theoretical prediction that patterns of excitatory input activitythat consistently fail to activate target neurons sufficiently to induce synaptic potentiation will instead cause a specific synaptic depression. To realize this situation experimentally, the Schaffer collateral projection to area CA1 in rat hippocampal slices was stimulated electrically at frequencies ranging from 0.5 to 50 Hz. Nine hundred pulses at 1-3 Hz consistently yielded a depression of the CA1 population excitatory postsynaptic potential that persisted without signs of recovery for > 1 hr after cessation of the conditioning stimulation. This long-term depression was specific to the conditioned input, ruling out generalized changes in postsynaptic responsiveness or excitability. Three lines of evidence suggest that this effect is accounted for by a modification of synaptic effectiveness rather than damage to or fatigue of the stimulated inputs.