Department of Psychiatry, UMC Utrecht, Rudolf Magnus Institute of Neuroscience, Utrecht, The Netherlands.
J Neurosci Methods. 2012 Jul 30;209(1):113-9. doi: 10.1016/j.jneumeth.2012.05.028. Epub 2012 Jun 5.
Although deep brain stimulation (DBS) has been proven to be an effective treatment for several neuropsychiatric disorders, such as Parkinson's disease, the underlying working mechanisms are still largely unknown. Behavioral animal models are essential in examining the working mechanisms of DBS and especially mouse models are necessary to investigate the genetic component underlying specific behaviors related to psychiatric diseases. Unfortunately, currently available stimulation devices are unsuitable to test behavior in freely-moving mice. As such, no DBS studies in behaving mice have been reported thus far. In order to overcome this limitation we have developed a new light-weight wireless implantable micro stimulator device for mice that delivers biphasic pulse patterns to two individual electrode pairs, mimicking partly the clinical situation. This paper describes in detail the bench-top validation and in vivo implementation of this device. The results in this study indicate that the wireless implantable stimulator in mice reliably delivers continuous bilateral stimulation, importantly, does not restrict the animals mobility and hygiene (grooming behavior). In vivo testing furthermore showed that stimulation of the mice ventral striatum yields similar results as previously shown by others in rats where conventional deep brain stimulation techniques were used. This newly designed device can now be used in the highly needed DBS behavioral studies in mice, to further investigate the underlying mechanisms of DBS in behavioral animal models for psychiatric disorders.
虽然深部脑刺激（DBS）已被证明是治疗几种神经精神疾病的有效方法，如帕金森病，但其潜在的工作机制仍在很大程度上未知。行为动物模型对于研究 DBS 的工作机制至关重要，特别是对于研究与精神疾病相关的特定行为的遗传成分，小鼠模型是必要的。不幸的是，目前可用的刺激设备不适合测试自由移动的小鼠的行为。因此，迄今为止，没有关于在活动小鼠中进行 DBS 研究的报道。为了克服这一限制，我们开发了一种新的用于小鼠的重量轻的无线植入式微刺激器设备，该设备可向两个单独的电极对传递双相脉冲模式，部分模拟临床情况。本文详细描述了该设备的台架验证和体内实施情况。本研究中的结果表明，无线植入式小鼠刺激器可靠地提供连续的双侧刺激，重要的是，不会限制动物的活动能力和卫生状况（梳理行为）。体内测试还表明，刺激小鼠腹侧纹状体产生的结果与以前使用传统深部脑刺激技术在大鼠中显示的结果相似。这个新设计的设备现在可以用于在小鼠中进行急需的 DBS 行为研究，以进一步研究深部脑刺激在精神疾病行为动物模型中的潜在机制。
