Aberrant Behaviour and Neural Activity in the 5xFAD Mouse Model of Alzheimer's Disease: Exploring Behavioural and Psychological Symptoms of Dementia in a Mouse Model of Amyloid Pathology

Abstract

The present work examines behavioural and psychological symptoms of dementia (BPSD)-like behaviours in the 5xFAD mouse model of Alzheimer’s disease (AD)-related amyloid pathology. In particular, this work reviews BPSD-like behaviours exhibited by transgenic mouse models of AD-related amyloid and tau pathology and suggests that apathy—particularly social withdrawal—and depression may be related to neuropathology, while aggression and sleep/wake disturbances appear to be present even at early ages. Similarly, an examination of social investigation and aggression in 5xFAD mice identified that 6-month-old 5xFAD females and males exhibit reduced social investigation compared to wild-type controls, and that altered arousal may underlie these effects; these effects are not mediated by the genotype of a novel conspecific. Additionally, cages housing only transgenic 5xFAD males are more likely to exhibit injuries arising from home-cage aggression than cages housing only wild-type males or both wild-type and transgenic males even though transgenic 5xFAD males do not exhibit an overt increase in aggression relative to wild-type controls in either novel or familiar environments. The present work also outlines the design, assembly, and function of a novel, open-source olfactometer that can be used with tethered or untethered rodents. This olfactometer was used to examine neural activity in the form of local field potential (LFP) in the medial prefrontal cortex (mPFC) of awake, behaving 5xFAD mice in response to social and non-social olfactory stimuli, identifying altered baseline and task-dependent neural activity in this area in transgenic 5xFAD mice. Overall, these findings provide an important step towards better understanding the interplay between aberrant neural activity and behavioural changes resulting from AD-related amyloid pathology.