CA1-specific N-methyl-D-aspartate receptor knockout mice are deficient in solving a nonspatial transverse patterning task

Abstract

In both humans and animals, the hippocampus is critical to memory across modalities of information (e.g., spatial and nonspatial memory) and plays a critical role in the organization and flexible expression of memories. Recent studies have advanced our understanding of cellular basis of hippocampal function, showing that N-methyl-d-aspartate (NMDA) receptors in area CA1 are required in both the spatial and nonspatial domains of learning. Here we examined whether CA1 NMDA receptors are specifically required for the acquisition and flexible expression of nonspatial memory. Mice lacking CA1 NMDA receptors were impaired in solving a transverse patterning problem that required the simultaneous acquisition of three overlapping odor discriminations, and their impairment was related to an abnormal strategy by which they failed to adequately sample and compare the critical odor stimuli. By contrast, they performed normally, and used normal stimulus sampling strategies, in the concurrent learning of three nonoverlapping concurrent odor discriminations. These results suggest that CA1 NMDA receptors play a crucial role in the encoding and flexible expression of stimulus relations in nonspatial memory.

Figure 1

Percent of subjects reaching the performance criterion (eight of nine correct choices) on each training session in (A) transverse patterning and (B) concurrent discrimination. *, χ²; P < 0.001.

Figure 2

Mean percent correct responses on each training session for odor pairs associated with worst (A and D), middle (B and E), and best (C and F) accurate performance. (A–C) The transverse patterning problem. (D–F) The concurrent discrimination problem. *, Significantly different from chance; ANOVA; P < 0.05. **, Significantly different from both chance level and the score for CA1-NR1 mice; ANOVA; P < 0.001.

Figure 3

Distribution of the number of odor cups visited per trial combined across all sessions of (A) transverse patterning and (C) concurrent discrimination, and the mean number of odor cups visited on individual training sessions in (B) transverse patterning and (D) concurrent discrimination. *, ANOVA, P < 0.007.