Spatial memory of heterozygous staggerer (Rora(+)/Rora(sg)) versus normal (Rora(+)/Rora(+)) mice during aging.

Heterozygous staggerer mice (Rora(+)/Rora(sg)) 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(+)/Rora(sg) mice. Previous studies showed that in both cases, neuronal number in the cerebellar cortex was normal. 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(+)/Rora(sg) 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(+)/Rora(sg) mice.