Cortico-cortical and hippocampal-cortical interactions in mouse models of Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disease which is pathologically characterized by extracellular deposition of amyloid beta (Aβ) plaques, intracellular deposition of neurofibrillary tangles (NFT) caused by hyperphosphorylated tau protein, neuroinflammation, and progressive neuron loss. Brain regions involved in memory processing, such as hippocampus and the neocortex, are affected in the early stages of disease pathology. Using in vivo mesoscale wide-field voltage imaging and local field potential (LFP) recording from CA1 region of the hippocampus in 6- and 12-month-old (1) knock-in (AppNL-G-F) and (2) transgenic (5xFAD) mouse model of AD, this study is aimed at understanding how cortico-cortical and hippocampal-cortical interactions are affected by AD. Aberrant sensory evoked cortical activity and resting state cortical functional connectivity were observed in AD and sharp wave ripples (SWRs), which subserve important aspects of hippocampal-cortical interactions are disrupted in AD. Further, gradual cerebral hypoperfusion exacerbate AD pathology and network dysfunctions.