Comparison of the performance of DBA/2 and C57BL/6 mice in transitive inference and foreground and background contextual fear conditioning

Abstract

DBA/2 mice have altered hippocampal structure and perform poorly in several hippocampus-dependent contextual/spatial learning tasks. The performance of this strain in higher cognitive tasks is less studied. Transitive inference is a hippocampus-dependent task that requires an abstraction to be made from prior rules to form a new decision matrix; performance of DBA/2 mice in this task is unknown, whereas contextual fear conditioning is a hippocampus-dependent task in which DBA/2 mice have deficits. The present study compared DBA/2J and C57BL/6J inbred mice in two different contextual fear conditioning paradigms and transitive inference to test whether similar deficits are seen across these hippocampus-dependent tasks. For background fear conditioning, mice were trained with two paired presentations of an auditory conditioned stimulus (CS, 30 seconds, 85 dB white noise) paired with an unconditioned stimulus (US, 2 seconds, 0.57 mA footshock), the context was a continuous background CS. Mice were tested for contextual learning 24 hours later. Foreground fear conditioning differed in that no auditory CS was presented. For transitive inference, separate mice were trained to acquire a series of overlapping odor discrimination problems and tested with novel odor pairings that either did or did not require the use of transitive inference. DBA/2 mice performed significantly worse than the C57BL/6 in both foreground and background fear conditioning and transitive inference. These results demonstrate that the DBA/2 mice have deficits in higher-cognitive processes and suggest that similar substrates may underlie deficits in contextual learning and transitive inference.

Figure 1

Performance in background (A) and foreground (B) contextual fear conditioning. In both cases the DBA/2 strain performed significantly poorer than the C57BL/6 strain. Asterisks represent significance between groups at p<0.05. Error bars represent ± the SEM.

Figure 2

Days to criterion. A) Days to acquire each phase shortened as time progressed. B) There was no significant difference between strains in total days to reach criteria. Error bars represent ± the standard error of the mean.

Figure 3

Performance on presented pairs during probe trials. There was a significant interaction between strain and pairing for percent correct. The DBA/2 strain performed better than the C57BL/6 strain when the pairing was B+C− and worse when the pairing was C+D−. Asterisks represent a significant main effect differences between strains. Furthermore, the C57BL/6 mice performed significantly worse on trials with pairing B+C− than trials with all other pairings, represented by the § symbol. The DBA/2 mice performed significantly better for trials with pairings B+C− and D+E− than ones with pairing C+D− and trials with pairing D+E− than ones with pairing A+B−. Within the DBA/2 strain, # represents a significant difference from D+E−; φ represents a significant difference from B+C−. All differences are at p<0.05. Error bars represent ± the standard error of the mean.

Figure 4

Performance on the novel pairs during probe trials. Performance was significantly different from chance for the C57BL/6 strain in both the novel transitive inference and control pairs but was only above chance for the DBA/2 strain in the novel control pair. DBA/2 strain performed significantly worse than the C57BL/6 strain in the novel transitive inference pair B vs D There were no differences between strains for the novel control pair A vs E. Error bars represent ± the standard error of the mean. Asterisks represent significance between groups at p<0.05. ‡ represents significantly different from chance.