Speaker: Dr Laura Bradfield (UTS)

Title: Hippocampal dysregulation causes transient deficits in decision-making: consequences for old age and Alzheimer’s disease

Abstract: The hippocampus is a central component of learning and memory systems in the brain, but its role in decision-making has received comparatively little attention. We found that, similar to its role in learning and memory, the hippocampus regulates goal-directed decision-making in a temporally transient manner. Specifically, we chemogenetically inactivated the dorsal CA1 region of the hippocampus in rats during outcome devaluation testing: the gold-standard test of goal-directed action in rodents. We found that such inactivation impaired goal-directed decisions on this test if it occurred immediately after initial training, but not after extended training or after a one week temporal window had passed. As degeneration of the hippocampus is observed in old age and in Alzheimer’s disease, we next investigated whether a similar temporal transience in decision-making impairments would be observed in aged mice, and a J20 mouse model of Alzheimer’s disease. Indeed we found that outcome devaluation performance was impaired after initial training in both aged and J20 mice relative to wildtype controls, but that this deficit could be overcome with additional training. Aged J20 mice showed an additional deficit in outcome-selective reinstatement. We further found strong relationships between neuroinflammatory markers in the dorsal CA1 region and goal-directed decision-making performance. Experiments investigating a causal connection between local neuroinflammation and goal-directed decision-making impairments are currently ongoing.