Impairment in novelty-promoted memory via behavioral tagging and capture before apparent memory loss in a knock-in model of Alzheimer's disease

Alzheimer's disease (AD) is associated with cognitive impairments and age-dependent memory deficits which have been studied using genetic models of AD. Whether the processes for modulating memory persistence are more vulnerable to the influence of amyloid pathology than the encoding and consolidation of the memory remains unclear. Here, we investigated whether early amyloid pathology would affect peri-learning novelty in promoting memory, through a process called behavioral tagging and capture (BTC). App(NL-G-F/NL-G-F) mice and wild-type littermates were trained in an appetitive delayed matching-to-place (ADMP) task which allows for the assessment of peri-learning novelty in facilitating memory. The results show that novelty enabled intermediate-term memory in wild-type mice, but not in App(NL-G-F/NL-G-F) mice in adulthood. This effect preceded spatial memory impairment in the ADMP task seen in middle age. Other memory tests in the Barnes maze, Y-maze, novel object or location recognition tasks remained intact. Together, memory modulation through BTC is impaired before apparent deficits in learning and memory. Relevant biological mechanisms underlying BTC and the implication in AD are discussed.

Automated summary

This study investigated the impact of early amyloid pathology on peri-learning novelty in memory promotion. The results showed that novelty facilitated intermediate-term memory in wild-type mice, but not in App(NL-G-F/NL-G-F) mice. This effect occurred before the spatial memory impairment observed in the ADMP task. Other memory tests remained intact.