Sex-specific interactions between procedural and deliberative decision-making systems in a mouse model of Alzheimer’s disease
Year: 2021
Type: preprint
Abstract: A central question in aging and Alzheimer’s 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 (Aβ) 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.
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Role of alpha-synuclein-dependent network hyperactivity in Lewy Body Dementia, Estrogen Facilitation of Female Drug Relapse, Alpha-synculein/tau coupling in Alzheimer's disease, AMP-Kinase as a target for neuroprotection in AD, Relating episodic memory and episodic future thinking in hippocampus, G9000144607, G9000177255
OpenAlex ID: W3138466606