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


CONCLUSIONS
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.
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.
Lars Emil
LE
Larsen
Swammerdam Institute of Life Sciences, University of Amsterdam, The Netherlands.
Wytse Jan
WJ
Wadman
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.
Pieter
P
van Mierlo
Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology (LCEN3), De Pintelaan 185, Blok B, Ghent University, BE-9000 Ghent, Belgium.
Jean
J
Delbeke
Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology (LCEN3), De Pintelaan 185, Blok B, Ghent University, BE-9000 Ghent, Belgium.
Annelies
A
Grimonprez
Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology (LCEN3), De Pintelaan 185, Blok B, Ghent University, BE-9000 Ghent, Belgium.
Bregt
B
Van Nieuwenhuyse
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.
Jeanelle
J
Portelli
Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology (LCEN3), De Pintelaan 185, Blok B, Ghent University, BE-9000 Ghent, Belgium.
Paul
P
Boon
Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology (LCEN3), De Pintelaan 185, Blok B, Ghent University, BE-9000 Ghent, Belgium.
Kristl
K
Vonck
Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology (LCEN3), De Pintelaan 185, Blok B, Ghent University, BE-9000 Ghent, Belgium.
Robrecht
R
Raedt
D000818:Animals; D006624:Hippocampus / Q000502:physiology*; D008124:Locomotion; D008297:Male; D009474:Neurons / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D055366:Synaptic Potentials; D014630:Vagus Nerve / Q000502:physiology; D055536:Vagus Nerve Stimulation
Dentate gyrus; EEG; Evoked potential; Neurophysiology; Rat; Vagus nerve stimulation