The hippocampus contributes to memory expression during transitive inference in mice

Abstract

There is substantial evidence that the hippocampus plays a role in transitive inference, the capacity to link overlapping memories and subsequently make novel judgments between elements of those memories that are only indirectly related. However, it is unclear whether the hippocampus is involved primarily during the original acquisition of the overlapping memories, or additionally during the flexible expression of those memories during transitive judgments. Here, we demonstrated that selective hippocampal damage produced after acquisition of the overlapping memories resulted in a severe impairment in subsequent transitive inference judgments, indicating that the hippocampus does play an important role beyond the initial learning phase. Furthermore, this study extends to mice a role for the hippocampus in transitive inference, as previously observed in other species.

Prefrontal cortex: Role in acquisition of overlapping associations and transitive inference

“…DeVito et al (2010) found that animals with hippocampal lesions and sham-operated controls exhibited the same pattern of performance on the odor pairs, such that performance on the context-dependent BC and CD discriminations was lower than performance on the AB and DE pairs; however, the animals with hippocampal damage exhibited higher levels of performance on the end-anchored (AB and DE) discriminations as compared to controls. In this study, both sham-operated animals and animals with prefrontal damage exhibited very different patterns of performance.…”

“…Recent studies have demonstrated that the hippocampus itself is initially critical to the transitive judgment ( Van der Jeugd et al 2009;DeVito et al 2010). DeVito et al (2010) found that damage to the hippocampus produced even after the animals had demonstrated successful transitive performance still impairs the ability to perform transitive inference; however, an additional 1-wk test revealed a partial recovery in relational memory abilities. In contrast to these results, Van der Jeugd et al (2009) demonstrated that damage to the hippocampus prior to learning, and not after the pairs had been learned, resulted in a deficit in transitive inference judgments.…”

“…Neither cup was baited during probe trials, and the amount of time the animals spent digging in each cup was used as the measure of transitive choice. These digging times were used to calculate a preference index (PI) (DeVito et al 2010). For the B vs. D test, PI ¼ (B -D)/ (B þ D); for A vs. E, PI ¼ (A 2 E)/(A þ E).…”

“…Transitive inference is a relational memory task that relies on the ability to integrate experiences sharing overlapping features and to use that information to guide judgments about those indirectly related experiences. Rats and monkeys with damage to the fornix, hippocampus, and perirhinal and entorhinal cortices can learn the items associated with a memory, but are impaired when asked to make judgments about those indirectly related items (Bunsey and Eichenbaum 1996;Dusek and Eichenbaum 1997;Buckmaster et al 2004; Van der Jeugd et al 2009;DeVito et al 2010). In humans, the hippocampus is activated when subjects perform transitive inference judgments (Heckers et al 2004;Zalesak and Heckers 2009).…”

Phencyclidine disturbs relational memory in the transitive inference task

“…Davis (1992) has developed this test version for rats. Although extensively used to evaluate the role of the hippocampus (Dusek and Eichenbaum, 1997;Eichenbaum et al, 1999;Devito et al, 2010a) and the prefrontal cortex (Devito et al, 2010b) in relational memory, to our knowledge this test has never been used to assess the effect of drugs affecting cognitive domains disturbed in schizophrenia. Phencyclidine (PCP) is a drug that produces a number of cognitive disturbances, including cognitive inflexibility .…”