Episodic-like memory is sensitive to both Alzheimer's-like pathological accumulation and normal ageing processes in mice.

Episodic memory depends on the hippocampus and is sensitive to both Alzheimer's disease (AD) pathology and normal ageing. We showed previously that 3xTgAD mice express a specific, episodic-memory deficit at 6 months of age in the What-Where-Which occasion (WWWhich) task (Davis, Easton, Eacott and Gigg, 2013). This task requires the integration of object-location and contextual cues to form an episodic-like memory. Here, we explore the cumulative effect of AD pathology on WWWhich memory by testing very young and middle-aged mice (3 and 12 months old, respectively). For comparison, we included an alternative episodic-like task (What-Where-When; WWWhen) and an object temporal order (Recency) task to explore claims that WWWhen types of memory are open to non-episodic solutions. We found that in contrast to their performance at 6 months, 3-month-old 3xTgAD mice formed WWWhich episodic-like memories; however, their performance at this age was poorer than in matched controls. In contrast, 3xTgAD and control animals aged 12 months were both impaired on the WWWhich task. Finally, 3xTgAD mice with a WWWhich deficit were unimpaired in both Recency and WWWhen tasks. These results support conclusions that: (1) young 3xTgAD mice express episodic-like memory, albeit depressed relative to controls; (2) age-related changes result in a deficit on the hippocampal-dependent WWWhich episodic memory task; and (3) control and 3xTgAD mice can use recency (trace strength) rather than episodic-like memory for tasks that contain a temporal 'When' component. These results, in combination with our previous findings, support an age-related decline in WWWhich episodic-like memory in mice. Furthermore, this decline is accelerated in the 3xTgAD model.