7. Project Summary: Dietary sugar consumption has dramatically risen in the U.S. over the past 60 years 1. In addition to being associated with body weight gain and harmful metabolic outcomes 2-7, emerging evidence reveals that excessive consumption of sugar and other “obesogenic” dietary factors (e.g., saturated fatty acids) negatively impacts memory function and other cognitive processes 8,9. Particularly concerning is the rise in sugar consumption among children, who with ~15-20% of their total daily caloric intake from added sugars (predominantly from sugar-sweetened beverages, SSBs) 10,11, are the highest sugar consumers of any age group. The juvenile and adolescent developmental phases are highly susceptible periods for the onset of metabolic dysfunction resulting from excessive sugar intake 6 and new evidence suggests that this period of development is also a particularly vulnerable time for sugar-related neurocognitive deficits 12,13. Therefore, it is important to understand the precise developmental periods and domains of cognition that are vulnerable to excessive consumption of added sugars during early life periods. Our preliminary data presented herein reveals that excessive consumption of SSBs (11% carbohydrate solution to match commonly consumed SSBs in the U.S.) in rats beginning at the onset of the juvenile period of development but not beginning during early adulthood impairs spatial memory function and increases neuroinflammation in the hippocampus 14, a brain region classically associated with spatial and declarative memory function and more recently with learned aspects of food intake control 15,16. Other preliminary data presented in this proposal offer insight into possible mechanisms linking early life sugar consumption with hippocampal-dependent memory impairments, as early life SSB access profoundly alters the gut microbiome and reduces markers of neurogenesis in the hippocampus. Proposed experiments will provide mechanistic insight into the relationship between early life sugar consumption and memory impairment by illuminating [1] the precise developmental periods and feeding- relevant memory processes that are particularly vulnerable to early life sugar consumption, [2] the underlying neurobiological mechanisms through which dietary factors during development influence cognition, and [3] intervention strategies that can potentially reverse the long-lasting memory deficits associated with excessive early life sugar consumption. Results will contribute toward understanding the underlying mechanisms through which obesogenic dietary factors influence cognition and may provide valuable insight toward reversing or preventing the pathological effects of unhealthy dietary factors on the brain.