Degenerate mapping of environmental location presages deficits in object-location encoding and memory in the 5xFAD mouse model for Alzheimer's disease

• DOI: 10.1016/j.nbd.2022.105939
• Publication Date: 2022-12-01T01:33:48Z
• Authors: Hai Zhang; Lujia Chen; Kevin G. Johnston; Joshua Crapser; Kim N. Green; Nicole My-Linh Ha; Andrea J. Tenner; Todd C. Holmes; Douglas A. Nitz; Xiangmin Xu
• Keywords: Memory Impairment; Neurophysiology

A key challenge in developing diagnosis and treatments for Alzheimer's disease (AD) is to detect abnormal network activity at as early a stage possible. To date, behavioral neurophysiological investigations AD model mice have yet conduct longitudinal assessment of cellular pathology, memory deficits, correlates neuronal activity. We therefore examined the temporal relationships between activities spatial representation environments, well object location deficits across multiple stages development 5xFAD compared these results those observed wild-type mice. performed vivo calcium imaging with miniscope on hippocampal CA1 neurons behaving find that show amyloid plaque accumulation, depressed during immobile states, degenerate unreliable neuron tuning environmental by 4 months age while their (OLM) comparable WT By 8 age, OLM, which are accompanied progressive degradation encoding and, eventually, impaired neural object-location pairings. Furthermore, correlated performance OLM 8-month-old. Our indicate close connection presence deficits. The also highlight baseline firing rates states precede predict older suggesting potential opportunities detecting.