Sanders Nichole C, Williams D Keith, Wenger Galen R
University of Arkansas Medical Sciences, Center for Addiction Research, Slot 611, 4301 W. Markham, Little Rock, AR 72205, USA.
Behav Brain Res. 2009 Oct 12;203(1):137-42. doi: 10.1016/j.bbr.2009.04.031. Epub 2009 May 3.
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.
Ts65Dn小鼠在16号染色体部分三体，被认为是人类唐氏综合征的有效小鼠模型。先前使用递增重复获得（IRA）强化程序的研究表明，与同窝对照相比，年轻和成年的Ts65Dn小鼠存在显著的学习缺陷。本研究的目的是检查这种缺陷在这些小鼠的生命周期中是否会发生变化。为了确定缺陷的变化是否由运动或动机缺陷引起，第二组小鼠在任务的表现版本（IRA-P）下接受训练以做出反应。IRA-P任务需要相同的运动反应来产生强化物，但不需要学习或获得。在IRA任务下收集的数据表明，与同窝对照相比，Ts65Dn小鼠存在持续到24个月龄的显著学习障碍。19个月龄后，Ts65Dn小鼠的反应率和获得的乳汁呈现次数显著下降。然而，在此期间，与运动能力和可能的动机无关的反应准确性并未下降。在IRA-P程序下，随着年龄增长，两个品系的乳汁呈现次数均未减少，但Ts65Dn小鼠的反应率趋势与在IRA任务下观察到的Ts65Dn小鼠的反应率趋势相似地下降。这些数据表明，通过IRA任务测量，Ts65Dn小鼠的学习能力不会随着年龄增长而下降，这表明Ts65Dn小鼠可能不会表现出人类患者中通常出现的相同早发性阿尔茨海默病表型。
