Vagal nerve stimulation induces vascular oscillations and enhances long-term learning

Despite its rapid emergence as a powerful approach for probing peripheral modulation of brain function, vagus nerve stimulation (VNS) is primarily understood through neuromodulatory pathways, leaving the potential contribution of vascular dynamics largely unexplored. Here, we examined whether VNS influences learning performance and its relationship with cerebrovascular dynamics using a chronic cuff-electrode system in freely moving mice. Using a cerebellum-dependent horizontal optokinetic response (HOKR) paradigm, we show that post-training VNS selectively enhances long-term learning. In parallel, in vivo fiber photometry reveals that VNS induces transient vascular fluctuations that evolve into oscillatory dynamics across repeated stimulation. The magnitude of these oscillations is increased by VNS and correlates with multi-day learning performance. These findings suggest that, in addition to neuromodulatory mechanisms, vascular dynamics may represent an underappreciated component of learning-related brain function. VNS-induced vascular oscillations are associated with multi-day learning, providing a new perspective on how peripheral signals influence central brain function.