Vagus nerve stimulation-induced cognitive enhancement: Hippocampal neuroplasticity in healthy male rats

Abstract

Background: Vagus nerve stimulation (VNS) improves cognition in humans and rodents, but the effects of a single session of VNS on performance and plasticity are not well understood.

Objective: Behavioral performance and hippocampal (HC) electrophysiology/neurotrophin expression were measured in healthy adult rats after VNS paired training to investigate changes in cognition and synaptic plasticity.

Methods: Platinum/iridium electrodes were surgically implanted around the left cervical branch of the VN of anesthetized male Sprague-Dawley rats (N = 47). VNS (100 μs biphasic pulses, 30 Hz, 0.8 mA) paired Novel Object Recognition (NOR)/Passive Avoidance Task (PAT) were assessed 24 h after training and post-mortem tissue was collected 48 h after VNS (N = 28). Electrophysiology recordings were collected using a microelectrode array system to assess functional effects on HC slices 90 min after VNS (N = 19). Sham received the same treatment without VNS and experimenters were blinded.

Results: Stimulated rats exhibited improved performance in NOR (p < 0.05, n = 12) and PAT (p < 0.05, n = 14). VNS enhanced long-term potentiation (p < 0.05, n = 7-12), and spontaneous spike amplitude (p < 0.05, n = 7-12) and frequency (p < 0.05, n = 7-12) in the CA1. Immunohistochemical analysis found increased brain-derived neurotrophic factor expression in the CA1 (p < 0.05, n = 8-9) and CA2 (p < 0.01, n = 7-8).

Conclusion: These findings suggest that our VNS parameters promote synaptic plasticity and target the CA1, which may mediate the positive cognitive effects of VNS. This study significantly contributes to a better understanding of VNS mediated HC synaptic plasticity, which may improve clinical utilization of VNS for cognitive enhancement.

Keywords: Brain-derived neurotrophic factor; Long-term potentiation; Novel object recognition; Passive avoidance; Spontaneous spiking; Synaptic plasticity; Vagus nerve stimulation.