An age‐related deficit in working memory emerges in the Ts65Dn mouse, a murine model of Down syndrome

Abstract

Previous research showed an initial deficit in working memory in young adult, male Ts65Dn mice compared to young adult, male littermate controls (LC). This deficit disappeared with additional training (Dowdy‐Sanders and Wenger, Behav. Brain Res. 168: 349‐352, 2006), suggesting a delayed learning curve rather than a true deficit in working memory. The purpose of this study was to determine the effect of age on working memory in male Ts65Dn and LC mice responding under a matching‐to‐position schedule of reinforcement. The mice were trained beginning at 3‐ months of age, and were tested until 24‐ months of age. Similar to the prior study, there was an initial deficit in the working memory of the Ts65Dn mice compared to LC that disappeared with practice. Once the initial deficit was reduced by additional training, the length of the mean delay for the session achieved by the two lines of mice was indistinguishable, and remained stable until after 20‐ months of age. Between 20‐ and 24‐months of age a difference in the mean delay for the session emerged between the two lines. These results suggest a difference in the cognitive decline of aged Ts65Dn mice compared to aged LC mice. Supported by NIH grant HD047656 (G.R.W.)