Rapid forgetting of social learning in the Ts65Dn mouse model of Down syndrome: New evidence for hippocampal dysfunction

Abstract

The Ts65Dn mouse model of Down syndrome recapitulates the hallmark areas of dysfunction that characterize the human disorder, including impaired performance in tasks designed to tap hippocampus-dependent learning and memory. Unfortunately, performance in the water maze tasks most commonly used for this purpose can be affected by behavioral and/or physiological abnormalities characteristic of Ts65Dn mice (e.g., thigmotaxis, susceptibility to hypothermia, stress reactivity), which complicates interpretation of impaired performance. The current study assessed hippocampal function in Ts65Dn mice using the social transmission of food preference (STFP) paradigm, which does not entail water escape or aversive reinforcement, and thus avoids these interpretive confounds. We tested Ts65Dn mice and disomic controls on this task using 1- and 7-day retention intervals. The Ts65Dn mice exhibited normal learning and memory following the 1-day retention interval, but rapid forgetting of the socially acquired information, evidenced by impaired performance following the 7-day retention interval. The STFP paradigm can be a valuable tool for studies using the Ts65Dn mouse model to evaluate potential therapies that may ameliorate hippocampal dysfunction and aging-related cognitive decline in Down syndrome. (PsycINFO Database Record

Figure 1. Percentage of cocoa-adulterated chow consumed during the STFP test, as a function of genotype, retention interval, and the diet consumed by the paired demonstrator (cocoa- or cinnamon-adulterated chow)

A significant social learning effect was observed for the 2N mice tested at a 1-day retention interval, the 2N mice tested at a 7-day retention interval, and the Ts65Dn mice tested at a 1-day retention interval (*p < 0.05). There was no significant social learning effect for the Ts65Dn mice tested at a 7-day retention interval (n.s.). Significant social learning was defined as a significant difference in the percent cocoa-adulterated chow consumed between the subgroup paired with a demonstrator fed cocoa chow versus the subgroup paired with a demonstrator who had consumed cinnamon chow. In addition, there was a significant effect of delay for the Ts65Dn mice paired with cinnamon demonstrators (#p < 0.05). Solid symbols = 2N mice, open symbols = Ts65Dn mice. Circles = mice paired with cocoa demonstrators, squares = mice paired with cinnamon demonstrators. Solid lines represent the median within each group.