Behavioral comparison of 4 and 6 month-old Ts65Dn mice: age-related impairments in working and reference memory.

Ts65Dn mice are partially trisomic for a segment of murine chromosome 16 similar to the gene segment on human chromosome 21 affected in Down's syndrome (DS). These animals display cognitive deficits, neurochemical imbalances, and cholinergic degeneration resembling alterations in DS and early onset Alzheimer's disease. The loss of basal forebrain cholinergic phenotype in Ts65Dn mice begins at approximately 6 months of age and may be due to an improperly functioning neurotrophic system. We compared 4 and 6 month-old Ts65Dn mice in a water-escape radial-arm maze task to investigate working and reference memory before and after the reported onset of cholinergic decline. Both 4 and 6 month-old Ts65Dn mice exhibited impaired performance compared to age-matched controls. However, the younger Ts65Dn mice displayed the capability to learn all working and reference memory measures, while the older Ts65Dn mice did not. Ts65Dn mice failed to maintain performance as working memory load increased, and the ability to handle an increasing working memory load also diminished with age. Collectively, these data suggest that major alterations in cognitive function occur in Ts65Dn mice between the ages of 4 and 6 months.