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Genetically modified mice lacking the glutamate receptor A (GluR-A) subunit of the AMPA receptor (GluR-[A.sup.-/-] mice) display normal spatial reference memory but impaired spatial working memory (SWM). This study tested whether the SWM impairment in these mice could be explained by a greater sensitivity to within-session proactive interference. The SWM performance of GluR-[A.sup.-/-] and wild-type mice was assessed during nonmatching-to-place testing under conditions in which potential proactive interference from previous trials was reduced or eliminated. SWM was impaired in GluR-[A.sup.-/-] mice, both during testing with pseudotrial-unique arm presentations on the radial maze and when conducting each trial on a different 3-arm maze, each in a novel testing room. Experimentally naive GluR-[A.sup.-/-] mice also exhibited chance performance during a single trial of spontaneous alternation. This 1-trial spatial memory deficit was present irrespective of the delay between the sample information and the response choice (0 or 45 min) and the length of the sample phase (0.5 or 5 min). These results imply that the SWM deficit in GluR-[A.sup.-/-] mice is not due to increased susceptibility to proactive interference. Keywords: AMPA receptors, LTP, hippocampus, spatial memory, mice

Acquisition and reversal of a spatial discrimination were assessed in an appetitive, elevated plus-maze task in 4 groups of mice: knockout mice lacking the AMPA receptor subunit GluR-A (GluR1), wild-type controls, mice with cytotoxic hippocampal lesions, and controls that had undergone sham surgery. In agreement with previous studies using tasks such as the water maze, GluR-[A.sup.-/-] mice were unimpaired during acquisition of the spatial discrimination task, whereas performance in the hippocampal group remained at chance levels. In contrast to their performance during acquisition, the GluR-[A.sup.-/-] mice displayed a mild deficit during reversal of the spatial discrimination and were profoundly impaired during discrete trial, rewarded-alternation testing on the elevated T maze. The latter result suggests a short-term, flexible spatial working memory impairment in GluR-[A.sup.-/-] mice, which might also underlie their mild deficit during spatial reversal.