DEEP BRAIN STIMULATION IN PARKINSON MODELS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。高频脑深部刺激(DBS)位于苍白球内侧核(GPI)、丘脑底核(STN)或丘脑，是一种用于减轻帕金森氏症症状的治疗方法。DBS的作用机制不是通过刺激GPI或STN，同时我们在正常和单侧MPTP处理的猴子身上记录了作为基底神经节输出目标的丘脑神经元的活动。我们还检查了丘脑中抑制性突触被激活时对功能代谢指标(FDG的PET测量)的影响，并继续评估长期给猴子服用鱼藤酮的影响。今年，我们在GPI中延长了刺激持续时间，并在STN中应用了1秒持续时间的DBS。在两只猴子中，这两种方法都对大多数受影响的丘脑神经元产生持续抑制作用，1秒DBS也是如此。我们还在一只动物的颈动脉注射MPTP后进行了刺激，而且这种抑制持续存在。我们继续给一只老年猴子服用鱼藤酮，现在已经在900多天的过程中总共服用了超过5100毫克。使用改进的Kluver板进行的行为测试显示没有缺陷，到目前为止，DTBZ摄取的PET扫描成像显示DA终末没有缺陷。最后，我们使用FDG摄取的PET成像，在DBS打开和关闭的情况下，测试抑制性突触激活将产生局部(代谢)活动增加的假设，就像兴奋性突触所做的那样。对于我们在相同刺激下进行6对刺激/关闭的动物，数据分析并不完整，但一只动物的3对刺激的初步数据显示，丘脑的信号略有增加，但并不显著，与我们的假设一致。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. High frequency deep brain stimulation (DBS) in the internal globus pallidus (GPi), subthalamic nucleus (STN), or thalamus is a treatment used to reduce symptoms of Parkinson's disease. The mechanism by which DBS works is not by stimulating in GPi or STN while we simultaneously recorded the activity of thalamic neurons that are the target of basal ganglia output, in normal and unilateral MPTP-treated monkeys. We also have examined the effect on functional metabolic measures (PET measurement of FDG) when inhibitory synapses are activated in the thalamus, and we have continued our evaluation of the effects of chronic administration of rotenone to monkeys. This year we extended the stimulus duration for stimulation in Gpi, and we applied 1 sec duration DBS in STN. Both produced continued inhibition of most thalamic neurons affected in 2 monkeys, as did 1 sec DBS. We also have stimulated after MPTP intracarotid injection in one animal, and the inhibition persists. We have continued administration of rotenone to one aged monkey and now have administered a total of more than 5100 mg over the course of more than 900 days. Behavioral testing using a modified Kluver board has shown no deficit, and PET scan imaging of DTBZ uptake has shown no deficit in DA terminals to date. Finally, we used PET imaging of FDG uptake with DBS on vs. OFF to test the hypothesis that activation of inhibitory synapses would produce an increase in regional (metabolic) activity, as excitatory synapses do. Data analysis is not complete for the animal in which we did 6 paired stimon/off with the same stimulus, but preliminary data for 3 pairs in one animal gave small, but insignificant increases in signal in the thalamus, consistent with our hypothesis.