Abstracts

Rationale: Vagal nerve stimulation (VNS) is an FDA-approved treatment for medically refractory partial epilepsy and depression. We recently demonstrated that VNS is able to elevate seizure threshold in the kindling model of limbic epileptogenesis in adult rats. However, the mechanism by which VNS modulates brain function is unknown. In this study, we sought to elucidate the mechanism underlying the VNS s action. Methods: we first investigated whether VNS is able to modify firing rate of amygdala neurons. Single-unit firing data were collected from 127 amygdala neurons in 3 VNS-implanted animals before, during and after VNS stimulation at various current intensities using the stimulation protocol commonly used in epileptic patients. Next, we sought to investigate the molecular consequences of VNS in amygdala/piriform cortex by examining the proteome of the postsynaptic density (PSD) using quantitative LC-MS/MS.Results: 1. We found that VNS induced rapid, transient but significant changes in firing rate of amygdala neurons, consistent with the idea that VNS may regulate the excitability of neurons within the amygdala. 2. We detected 425 proteins in the PSD, consistent with similar prior studies. Furthermore, thirty-five proteins were differentially expressed by greater than 1.5-fold in VNS-treated animals. Conclusions: These results indicate that VNS is capable of modulating both the excitability and synaptic proteome of CNS neurons. Furthermore, our discovery provides clues to the mechanisms by which VNS modifies brain function.