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

Modulation of Hippocampal Activity by Vagus Nerve Stimulation in Freely Moving Rats
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DOI:
10.1016/j.brs.2015.09.009
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发表时间:
2016-01-01
期刊:
影响因子:
7.7
通讯作者:
Raedt, Robrecht
Raedt, Robrecht
中科院分区:
医学1区
文献类型:
--
作者:
Larsen, Lars Emil;Wadman, Wytse Jan;Raedt, Robrecht

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背景:迷走神经刺激(VNS)具有抑制癫痫发作的作用,但其机制尚不完全清楚。为进一步从神经生理学水平阐明VNS抑制癫痫发作的机制,本研究采用齿状回诱发电位(EPs)和海马脑电图(EEG)检测VNS对海马兴奋性的影响。将双极刺激电极植入左侧穿支通路,将双极记录电极植入左侧齿状回,记录EEG和齿状野EP。恢复后,在自由活动的动物中应用VNS,使用7 s开/18 s关的占空比,30 Hz频率,250 mu s脉冲宽度,以及0(SHAM),25 mu A或1000 mu A的强度,同时连续监测EEG和齿状场EP。VNS在1000 μ A调制齿状场EP通过降低场兴奋性突触后电位(fEPSP)斜率和增加群体尖峰的潜伏期和振幅。它还通过将θ节律从7 Hz减慢至5 Hz并降低θ峰和伽马带功率来影响海马EEG。结论:VNS对自由活动大鼠海马兴奋性具有复杂的调节作用。它降低了突触效能,反映在降低fEPSP斜率和EEG功率,但它同时促进了齿状颗粒细胞放电,表明齿状颗粒细胞的去极化。(C)2015 Elsevier Inc. All rights reserved.
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 mu s pulse width, and an intensity of either 0 (SHAM), 25 mu A or 1000 mu A, while continuously monitoring EEG and dentate field EPs.Results: VNS at 1000 mu A 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 mu A 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. (C) 2015 Elsevier Inc. All rights reserved.