Work

Vagus nerve stimulation enhances memory and long-term potentiation via the hippocampal NE/β-AR signaling pathway in pilocarpine rats

Year: 2026

Type: article

Abstract: BACKGROUND: Memory deficits in temporal lobe epilepsy severely impair quality of life, yet effective therapeutic strategies remain limited. Vagus nerve stimulation (VNS), an FDA approved treatment for drug resistant epilepsy, has demonstrated beneficial effects on cognition, but the underlying mechanisms are unclear. VNS activates the locus coeruleus norepinephrine (NE) system, and hippocampal β-adrenergic receptors (β-AR) are critical for memory formation and synaptic plasticity. In this study, we used a pilocarpine (PILO) induced memory impaired rodent model to investigate whether VNS improves memory and hippocampal synaptic plasticity via NE/β-AR signaling. METHODS: Memory impairment was induced in rats using PILO. VNS was administered to PILO-treated rats for 2 weeks via electrodes implanted on the left cervical vagus nerve (parameters: 1 mA, 30 Hz, 250 µs pulse width; 2 h daily). Following VNS treatment, rats underwent contextual fear conditioning (CFC) and long-term potentiation (LTP) testing. Protein expression of NE, β-AR, and downstream signaling molecules (protein kinase A and CaMKII) was quantified. To verify pathway specificity, the β-AR antagonist propranolol (PR) was administered RESULTS: PILO-treated rats exhibited significant memory deficits and impaired LTP compared to controls. VNS treatment markedly improved CFC performance and restored hippocampal LTP in PILO rats. Molecular analysis revealed VNS increased hippocampal NE release and upregulated β-AR and downstream signaling molecules PKA expression. Administration of β-AR antagonist PR prior to VNS abolished these enhancements in memory and synaptic plasticity. CONCLUSION: The enhancement of hippocampal LTP and memory by VNS is associated with the hippocampal NE/β-AR signaling pathway, indicating a potential therapeutic mechanism for VNS in memory related disorders.

Source: Brain Research Bulletin

DOI: 10.1016/j.brainresbull.2026.111789