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Authors & Affiliations
Philip Gade Knak, Rune Nguyen Rasmussen, Tatsushi Yokoyama, Masayuki Sakamoto, Maiken Nedergaard, Hajime Hirase, Antonis Asiminas
Abstract
Understanding the cellular mechanisms underlying learning and their alteration in Alzheimer’s disease (AD) is crucial for developing targeted therapies. We aimed to elucidate coordinated astrocytic and neuronal activities in learning, with a specific focus on their dynamics influenced by experience and alterations in AD. Using calcium imaging of neurons and astrocytes in the APP/PS1 double transgenic Alzheimer’s disease mouse model, we investigated behavioural and cellular responses to repetitive visual stimuli, in comparison with littermate wild type (WT) mice.We collected data from 32 female and male mice. Our findings revealed that while WT mice exhibited progressively decreased arousal to repetitive visual stimuli over seven days, consistent with prior studies, mice exposed to random stimuli showed no significant behavioural changes. Intriguingly, APP/PS1 mice did not show habituation to repetitive visual stimuli. This was mirrored in a distinct pattern of astrocytic activity, particularly a reduction in calcium activity in APP/PS1 mice astrocytes, notable only on the final day of the visual habituation protocol.These results highlight a unique, experience-dependent astrocytic activity phenotype in the APP/PS1 mouse model of AD, suggesting altered cellular mechanisms. We are currently expanding upon these initial findings through in-depth imaging data analysis. Future research directions include investigating molecular changes that may underlie the abnormal cellular response to novelty habituation in APP/PS1 mice.