Modulation of Hippocampal Activity by Vagus Nerve Stimulation in Freely Moving Rats

Lars Emil Larsen; Wytse Jan Wadman; Pieter van Mierlo; Jean Delbeke; Annelies Grimonprez; Bregt Van Nieuwenhuyse; Jeanelle Portelli; Paul Boon; Kristl Vonck; Robrecht Raedt

doi:10.1016/j.brs.2015.09.009

Modulation of Hippocampal Activity by Vagus Nerve Stimulation in Freely Moving Rats

Brain Stimul. 2016 Jan-Feb;9(1):124-32. doi: 10.1016/j.brs.2015.09.009. Epub 2015 Sep 25.

Authors

Affiliations

¹ Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology (LCEN3), De Pintelaan 185, Blok B, Ghent University, BE-9000 Ghent, Belgium. Electronic address: larsemil.larsen@ugent.be.
² Swammerdam Institute of Life Sciences, University of Amsterdam, The Netherlands.
³ Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology (LCEN3), De Pintelaan 185, Blok B, Ghent University, BE-9000 Ghent, Belgium; Department of Electronics and Information Systems, Medical Imaging and Signal Processing, Ghent University - iMinds Medical IT Department, Belgium.
⁴ Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology (LCEN3), De Pintelaan 185, Blok B, Ghent University, BE-9000 Ghent, Belgium.
⁵ Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology (LCEN3), De Pintelaan 185, Blok B, Ghent University, BE-9000 Ghent, Belgium; Department of Pharmaceutical Chemistry, Drug Analysis & Drug Information, Center for Neurosciences, Vrije Universiteit Brussel, Belgium.

PMID: 26481670
DOI: 10.1016/j.brs.2015.09.009

Abstract

Background: Vagus Nerve Stimulation (VNS) has seizure-suppressing effects but the underlying mechanism is not fully understood. To further elucidate the mechanisms underlying VNS-induced seizure suppression at a neurophysiological level, the present study examined effects of VNS on hippocampal excitability using dentate gyrus evoked potentials (EPs) and hippocampal electroencephalography (EEG).

Methods: Male Sprague-Dawley rats were implanted with a VNS electrode around the left vagus nerve. A bipolar stimulation electrode was implanted in the left perforant path and a bipolar recording electrode was implanted in the left dentate gyrus for EEG and dentate field EP recording. Following recovery, VNS was applied in freely moving animals, using a duty cycle of 7 s on/18 s off, 30 Hz frequency, 250 µs pulse width, and an intensity of either 0 (SHAM), 25 µA or 1000 µA, while continuously monitoring EEG and dentate field EPs.

Results: VNS at 1000 µA modulated dentate field EPs by decreasing the field excitatory post-synaptic potential (fEPSP) slope and increasing the latency and amplitude of the population spike. It additionally influenced hippocampal EEG by slowing theta rhythm from 7 Hz to 5 Hz and reducing theta peak and gamma band power. No effects were observed in the SHAM or 25 µA VNS conditions.

Conclusion: VNS modulated hippocampal excitability of freely moving rats in a complex way. It decreased synaptic efficacy, reflected by decreased fEPSP slope and EEG power, but it simultaneously facilitated dentate granule cell discharge indicating depolarization of dentate granule cells.

Keywords: Dentate gyrus; EEG; Evoked potential; Neurophysiology; Rat; Vagus nerve stimulation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Hippocampus / physiology*
Locomotion
Male
Neurons / physiology
Rats
Rats, Sprague-Dawley
Synaptic Potentials*
Vagus Nerve / physiology
Vagus Nerve Stimulation*