Consumption of a Western diet (WD) during early developmental stages is linked to memory problems, particularly affecting processes reliant on the hippocampus (HPC). To explore the neurobiological reasons behind this, Hayes et al. (2024) established a rodent model where early exposure to WD led to enduring dysfunction in the HPC. Rats were given either a cafeteria-style WD with unrestricted access to high-fat/high-sugar foods (CAF) or standard healthy chow (CTL) during their juvenile and adolescent phases (postnatal days 26–56). Behavioral and metabolic assessments were conducted before and after a period of healthy diet intervention starting in early adulthood. The results showed persistent deficits in contextual episodic memory in CAF rats, indicating HPC involvement. Since disrupted acetylcholine (ACh) signaling in the HPC is associated with memory problems, the authors examined ACh-related protein markers in CAF and CTL rats’ dorsal HPC (HPCd). Lower levels of vesicular ACh transporter protein were found in the HPCd of CAF rats compared to CTL rats, suggesting chronically reduced ACh levels. Using an intensity-based ACh sensing fluorescent reporter (iAChSnFr) in vivo fiber photometry targeted at the HPCd, the authors discovered that ACh release during object-contextual novelty recognition was strongly linked to memory performance and was impaired in CAF rats compared to CTL rats. Neuropharmacological experiments demonstrated that infusion of an alpha 7 nicotinic ACh receptor agonist into the HPCd during training restored memory deficits in CAF rats. Overall, these results highlight a functional relationship between early WD consumption and persistent dysregulation of HPC ACh signaling, providing insight into the mechanism underlying WD-related memory issues.
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