Journal Article Research Support, Non-U.S. Gov't Epublish 6 citations
PubMed: 36650070 DOI: 10.1523/ENEURO.0363-22.2023
Goal-Directed Action Is Initially Impaired in a hAPP-J20 Mouse Model of Alzheimer's Disease.
eNeuro 10(2)
Authors: Amolika Dhungana, Serena Becchi, Jessica Leake, Gary Morris, Nesli Avgan, Bernard W Balleine, Bryce Vissel, Laura A Bradfield
Affiliations
- School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, New South Wales 2007, Australia.
- Centre for Neuroscience and Regenerative Medicine, St. Vincent's Centre for Applied Medical Research, St. Vincent's Health Network, Sydney, New South Wales 2010, Australia.
- School of Psychology, University of New South Wales Sydney, Sydney, New South Wales 2052, Australia.
- Tasmanian School of Medicine, College of Health and Medicine, University of Tasmania, Hobart, Tasmania 7000, Australia.
- Decision Neuroscience Laboratory, School of Psychology, University of New South Wales Sydney, Sydney, New South Wales 2052, Australia.
- Centre for Neuroscience and Regenerative Medicine, St. Vincent's Centre for Applied Medical Research, St. Vincent's Health Network, Sydney, New South Wales 2010, Australia.
- School of Clinical Medicine, University of New South Wales Medicine & Health, St Vincent's Healthcare Clinical Campus, Faculty of Medicine and Health, University of New South Wales Sydney, Sydney, New South Wales 2052, Australia.
- School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, New South Wales 2007, Australia.
Abstract
Cognitive-behavioral testing in preclinical models of Alzheimer's disease has failed to capture deficits in goal-directed action control. Here, we provide the first comprehensive investigation of goal-directed action in a transgenic mouse model of Alzheimer's disease. Specifically, we tested outcome devaluation performance in male and female human amyloid precursor protein (hAPP)-J20 mice. Mice were first trained to press left and right levers for pellet and sucrose outcomes, respectively (counterbalanced), over 4 d. On test, mice were prefed one of the outcomes to satiety and given a choice between levers. Devaluation performance was intact for 36-week-old wild-types of both sexes, who responded more on the valued relative to the devalued lever (Valued > Devalued). By contrast, devaluation was impaired (Valued = Devalued) for J20 mice of both sexes, and for 52-week-old male mice regardless of genotype. After additional lever press training (i.e., 8-d lever pressing in total), devaluation was intact for all mice, demonstrating that the initial deficits were not a result of a nonspecific impairment in reward processing, depression, or locomotor activity in J20 or aging mice. Follow-up analyses revealed that microglial expression in the dorsal CA1 region of the hippocampus was associated with poorer outcome devaluation performance on initial, but not later tests. Together, these data demonstrate that goal-directed action is initially impaired in J20 mice of both sexes and in aging male mice regardless of genotype, and that this impairment is related to neuroinflammation in the dorsal CA1 hippocampal region.
MeSH
Hippocampus, Alzheimer Disease, Aging, Genotype, Nervous System Diseases