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bioRxiv · 10.1101/2021.03.16.435712

Sex-specific interactions between procedural and deliberative decision-making systems in a mouse model of Alzheimer's disease

Anderson, R.·Hart, D. W.·Sweis, B.·Sherman, M. A.·Thomas, M.·Redish, D. D.·Lesne, S.
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Abstract

A central question in aging and Alzheimers disease (AD) is when and how neural substrates underlying decision-making are altered. Here we show that while APP mice, a commonly used mouse model of AD, were able to learn Restaurant Row, a complex neuroeconomic decision-making task, they were significantly impaired in procedural, habit-forming, aspects of cognition and relied heavily on deliberation when making decisions. Surprisingly, these behavioral changes are associated with amyloid-beta (A{beta}) pathology and network remodeling in the striatum, a key brain region involved in procedural cognition. Furthermore, APP mice and control mice relied on distinct sex-specific strategies in this neuroeconomic task. These findings provide foundational pillars to examine how aging and age-related neurodegenerative diseases impact decision-making across sexes. They also highlight the need for complex behavioral tasks that allow for the dissociation of competing neurally-distinct decision-making circuits to get an accurate picture of changes in neurodegenerative models of human disease.

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Anderson, R., Hart, D. W., Sweis, B., Sherman, M. A., Thomas, M., Redish, D. D., Lesne, S.. 2021-03-17. Sex-specific interactions between procedural and deliberative decision-making systems in a mouse model of Alzheimer's disease. https://doi.org/10.1101/2021.03.16.435712

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