Research reportOlfactory delayed matching to sample performance in mice: Sex differences in the 5XFAD mouse model of Alzheimer's disease

•This is the first successful study of olfactory working memory in mice.•Mice learned an olfactory delayed matching to sample task with delays up to 30 s.•The 5XFAD mouse model showed no deficits in olfactory working memory at 6 months.•Female mice performed better than males on the olfactory working memory task.

While olfactory delayed matching-to-sample tasks have been used to assess working memory in rats, no such tasks have been tested in mice. Olfactory delayed matching-to-sample learning was assessed in male and female 5XFAD mice, a model of Alzheimer's disease, and their wildtype (B6SJL F1) littermates at 6-7 months of age using an operant olfactometer. All 5XFAD and wildtype mice were able to learn the delayed olfactory matching-to-sample task at 2 and 5 s delays. Fewer mice learned with a 10 s delay and only one mouse learned with a 30 s delay. Female mice showed higher levels of performance on the delayed matching-to-sample task than males, indicative of better working memory. These results demonstrate for the first time that mice are able to learn an olfactory delayed matching to sample task.