Does the learning deficit observed under an incremental repeated acquisition schedule of reinforcement in Ts65Dn mice, a model for Down syndrome, change as they age?

Abstract

The Ts65Dn mouse is partly trisomic at chromosome 16 and is considered to be a valid mouse model of human Down syndrome. Prior research using an incremental repeated acquisition (IRA) schedule of reinforcement has revealed that there is a significant learning deficit in young, adult Ts65Dn mice compared to littermate controls. The purpose of this study was to examine whether this deficit changes during the life-span of these mice. In order to determine if changes in the deficit were caused by motoric or motivational deficiencies, a second group of mice was trained to respond under a performance version of the task (IRA-P). The IRA-P task required the same motor responses to produce the reinforcer, but no learning or acquisition was required. Data collected under the IRA task demonstrated that there was a significant learning impairment that persisted up to 24 months of age in the Ts65Dn mice compared to littermate controls. There was a significant decrease in the rate of responding and the number of milk presentations earned by the Ts65Dn mice after 19 months of age. However, during this time, response accuracy, which is independent of mobility and possibly motivation, did not decrease. Under the IRA-P schedule, there was no decrease observed in the number of milk presentations of either line as they aged, but the trend in the rate of responding of the Ts65Dn mice was similarly declining as the rate of responding observed in the Ts65Dn mice under the IRA task. These data indicate that the ability to learn in Ts65Dn mice does not decline with age as measured by the IRA task and suggests that perhaps Ts65Dn mice do not exhibit the same early onset Alzheimer's disease phenotype that is typically seen in human patients.