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

Abstract

AbstractAlzheimer’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). AppNL-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 AppNL-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.