Ts65Dn mice, a model for Down syndrome, have deficits in context discrimination learning suggesting impaired hippocampal function

Abstract

The Ts65Dn mouse is segmentally trisomic for a part of mouse chromosome 16 and is a genetic model for Down syndrome and Alzheimer's disease. Although many studies have examined the learning and memory processes in Ts65Dn mice, it has yet to be determined if Ts65Dn mice are specifically impaired in learning tasks that require an intact hippocampus. Context discrimination learning is dependent on the dorsal hippocampus in mice. In this task, mice learn to discriminate two similar contexts, one of which is associated with foot shock. In the current study, Ts65Dn mice learned almost identically to what has been reported for mice with dorsal hippocampal lesions, while controls behaved similarly to sham lesioned mice. Therefore, Ts65Dn mice have learning deficits in a hippocampal dependent task that may be related to the loss of cholinergic input to the hippocampus, which occurs after 6 months of age.