Aberrant Cortical Activity in 5xFAD Mice in Response to Social and Non-Social Olfactory Stimuli

摘要

Background: Neuroimaging studies investigating the behavioral and psychological symptoms of dementia (BPSD)—such as apathy, anxiety, and depression—have linked some of these symptoms with altered neural activity. However, inconsistencies in operational definitions and rating scales, limited scope of assessments, and poor temporal resolution of imaging techniques have hampered human studies. Many transgenic (Tg) mouse models of Alzheimer's disease (AD) exhibit BPSD-like behaviors concomitant with AD-related neuropathology, allowing examination of how neural activity may relate to BPSD-like behaviors with high temporal and spatial resolution. Objective: To examine task-dependent neural activity in the medial prefrontal cortex (mPFC) of AD-model mice in response to social and non-social olfactory stimuli. Methods: We previously demonstrated age-related decreases in social investigation in Tg 5xFAD females, and this reduced social investigation is evident in Tg 5xFAD females and males by 6 months of age. In the present study, we examine local field potential (LFP) in the mPFC of awake, behaving 5xFAD females and males at 6 months of age during exposure to social and non-social odor stimuli in a novel olfactometer. Results: Our results indicate that Tg 5xFAD mice exhibit aberrant baseline and task-dependent LFP activity in the mPFC—including higher relative delta (1-4 Hz) band power and lower relative power in higher bands, and overall stronger phase-amplitude coupling—compared to wild-type controls. Conclusions: These results are consistent with previous human and animal studies examining emotional processing, anxiety, fear behaviors, and stress responses, and suggest that Tg 5xFAD mice may exhibit altered arousal or anxiety.