Four related experiments studied operant performance of mice on differential reinforcement of low rates of responding (DRL) paradigms. Experiment 1 showed that excitotoxic hippocampal lesions impaired performance of a 10-s DRL schedule (DRL-10). Experiments 2 and 3 showed that GluR-A AMPA receptor subunit knockout mice, which are deficient in CA3-CA1 long-term potentiation (LTP), were markedly impaired at 15 s (DRL-15), but less impaired at DRL-10. Experiment 4 compared DRL-15 performance in mice from the 2 strains from which the GluR-A colony was derived and showed that they did not differ. The results show that GluR-A-containing AMPA receptors are required for normal performance on hippocampus-dependent, nonspatial working memory tasks, consistent with a role for GluR-A in the temporal encoding (what happened when) of nonspatial information.