The vagus nerve promotes memory in rats via nutrient-induced septo-hippocampal acetylcholine signaling

The vagus nerve relays critical metabolic information between the gastrointestinal tract and the brain. Recent findings highlight a role for vagus nerve-mediated gut-brain signaling in regulating higher-order cognitive processes, although the underlying mechanisms remain poorly understood. Here we demonstrate in male rats that nutrient consumption promotes hippocampal-dependent memory function via vagus nerve-mediated acetylcholine (ACh) release in the dorsal hippocampus (HPCd) from medial septum (MS) neurons. In vivo fiber photometry analyses reveal that HPCd ACh release is engaged during nutrient consumption. This response was abolished in animals that received MS cholinergic neuron ablation, subdiaphragmatic vagotomy (SDV), or early-life Western Diet (WD) maintenance. MS cholinergic neuron ablation, SDV, and WD impaired memory for meal location, suggesting that this signaling pathway functions to promote memories for eating events. Collectively, results identify a neurobiological mechanism whereby nutrient consumption enhances memory function and suggest that disruption of this vagal-brain signaling system mediates WD-associated memory impairments.