DEEP BRAIN STIMULATION IN PARKINSON MODELS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。在内部苍白球（GPi）、丘脑下核（STN）或丘脑中进行高频深部脑刺激（DBS）是一种用于减轻帕金森病症状的治疗方法。在正常和单侧mptp治疗的猴子中，DBS的工作机制不是通过刺激GPi或STN，同时我们记录了丘脑神经元的活动，这些神经元是基底神经节输出的目标。我们还研究了丘脑中抑制性突触被激活时对功能性代谢测量（FDG的PET测量）的影响，并继续评估了长期给药鱼藤酮对猴子的影响。今年我们延长了Gpi刺激的刺激时间，在STN中应用了1秒持续DBS。这两种方法都对两只猴子的丘脑神经元产生了持续的抑制作用，1秒DBS也是如此。我们也在一只动物颈动脉内注射MPTP后进行了刺激，抑制仍然存在。我们继续给一只年老的猴子服用鱼藤酮，现在在900多天的时间里总共服用了5100多毫克。使用改进的Kluver板的行为测试显示没有缺陷，PET扫描成像显示DTBZ摄取到目前为止在DA终端没有缺陷。最后，我们使用PET成像的FDG摄取与DBS打开和关闭来验证假设，抑制性突触的激活会产生区域（代谢）活动的增加，因为兴奋性突触。对于我们用相同的刺激进行6对刺激/关闭的动物，数据分析不完整，但在一只动物中进行3对刺激/关闭的初步数据显示，丘脑信号的增加很小，但不显著，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.