Heterozygous staggerer mice (Rora+/Rorasg) and control mice (Rora+/Rora+) of the same C57BL/6J strain background were tested in a spontaneous alternation task at 3 to 24 months old. The results demonstrated a decrement in long-term working memory as early as 6 months in Rora+/Rora+ mice and at 3 months in Rora+/Rorasg mice. Previous studies showed that in both cases, neuronal number in the cerebellar cortex was normal (Doulazmi et al. [1999]). This suggests that age-dependent decrease in long-term working memory would be due to fine structural or biochemical changes preceding neuronal death in the cerebellum. Such subtle changes would occur more precociously in Rora+/Rorasg than in Rora+/Rora+ mice. Also, short-term working memory was preserved in Rora+/Rora+ mice as old as 24 months, but was impaired in 6-month-old Rora+/Rorasg mice.
