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.