Programmed deep brain stimulation synchronizes VTA gamma band field potential and alleviates depressive-like behavior in rats
Programmed deep brain stimulation synchronizes VTA gamma band field potential and alleviates depressive-like behavior in rats
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DOI：
10.1016/j.neuropharm.2014.12.003
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发表时间：
2015-04-01
影响因子：
4.7
通讯作者：
Yadid, Gal
中科院分区：
文献类型：
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作者：
Gazit, Tomer;Friedman, Alexander;Yadid, Gal
脑深部电刺激（DBS）可显著缓解各种神经系统疾病的症状。目前的研究重点是开发针对个体症状定制的程序化刺激方案。然而，程序性脑深部脑刺激（pDBS）的治疗机制尚不清楚。我们之前在弗林德斯敏感系（FSL）抑郁症大鼠模型中证明，腹侧被盖区（VTA）的pDBS使分子和行为异常正常化。在此，我们研究了短时间低频DBS模板对FSL大鼠VTA前后轴局部场电位（LFP）同步模式的影响，以及与非程序化连续低频DBS （npDBS）相比，这种影响与抑郁样行为的相关性。我们使用小波相位相干（WPC）测量来有效表征LFP模式的时间和频率，并使用强迫游泳测试来测量不动（绝望）。与SD对照组相比，FSLs的基线WPC值在低和高伽马频率范围（高于30 Hz）较低。FSL大鼠的基线不动评分高于SD大鼠，而pDBS而非npDBS显著降低FSL不动评分以控制SD水平，直至第14天。pDBS还显著增加了（从基线到第14天之间）β、低伽马和高伽马频率范围内WPC值的变化。高伽马（60-100 Hz） WPC值的改变与抑郁样行为的改善相关。我们的研究结果表明，VTA程序化的DBS增加了局部神经元群之间的相互作用，这种效应可能是抑郁样行为正常化的基础。(C) 2014 Elsevier Ltd.版权所有。
Deep brain stimulation (DBS) significantly alleviates symptoms in various neurological disorders. Current research focuses on developing programmed stimulation protocols for customization to individual symptoms. However, the therapeutic mechanism of action of programmed DBS (pDBS) is poorly understood. We previously demonstrated that pDBS in the ventral tegmental area (VTA) normalizes molecular and behavioral abnormalities in the Flinders Sensitive Line (FSL) rat model for depression. Herein, we examined the effect of a short-duration, low-frequency DBS template on local field potential (LFP) synchronization patterns along the anterior posterior axis of the VTA of FSL rats, and correlation of this effect with depressive-like behavior, as compared with non-programmed, continuous low-frequency DBS (npDBS). We used the wavelet phase coherence (WPC) measure for effective representation of time and frequency of LFP patterns, and the forced swim test to measure immobility (despair). Baseline WPC values were lower in FSLs as compared with SD controls, at the low and high gamma frequency range (above 30 Hz). Baseline immobility scores for FSL rats were higher than those of SD rats, while pDBS, and not npDBS, significantly reduced FSL immobility scores to control SD levels, up to day 14. pDBS also significantly increased the change (between baseline and day 14) in WPC values, in beta, low gamma and high gamma frequency ranges. The change in high gamma (60-100 Hz) WPC values correlated with improvement in depressive-like behavior. Our results suggest that programmed DBS of the VTA increases interaction among local neuronal populations, an effect that may underlie the normalization of depressive-like behavior. (C) 2014 Elsevier Ltd. All rights reserved.