DEEP BRAIN STIMULATION IN PARKINSON MODELS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。在内部苍白球（GPi），丘脑底核（BVI）或丘脑中的高频脑深部刺激（DBS）是用于减轻帕金森病症状的治疗方法。DBS工作的机制不是通过刺激GPi或GPi，而我们同时记录了正常和单侧MPTP治疗的猴中基底神经节输出靶向的丘脑神经元的活动。我们还检查了功能代谢措施（PET测量FDG）时，抑制性突触在丘脑中被激活的影响，我们继续我们的长期管理的影响鱼藤酮猴子的评价。 今年，我们延长了Gpi刺激的刺激持续时间，并在Gpi中应用了1秒持续时间的DBS。这两个产生持续抑制大多数丘脑神经元受影响的2只猴子，1秒DBS。我们还刺激了一只动物的颈动脉内注射MPTP后，抑制持续存在。 我们继续给一只年老的猴子服用鱼藤酮，现在已经在900多天的时间里总共服用了5100多毫克。使用改良Kluver板的行为测试显示无缺陷，DTBZ摄取的PET扫描成像显示迄今为止DA末端无缺陷。 最后，我们使用PET成像的FDG摄取与DBS上与关闭测试的假设，抑制性突触的激活会产生增加区域（代谢）活动，兴奋性突触。对于我们用相同刺激进行6对刺激/关闭的动物，数据分析是不完整的，但是一只动物中3对的初步数据给出了丘脑中信号的小但不显著的增加，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.