实时钙成像研究脑深部电刺激治疗帕金森病的机制

Parkinson's disease (PD) is one of the most common neurodegenerative disease, which damages the health of middle aged and elderly people. Deep brain stimulation (DBS) efficiently improve the motor functions of PD patients. Recently, the studies indicated DBS might inhibit the disorder of basal ganglia-cortex network. However, how the stimulated neurons responses during DBS is still not clear. In previous study, we found subthalamic DBS inhibited the expression of calcium-bingding protein "Calbindin-28" in basal ganglia output nucleus of 6-OHDA injuried PD rats, which indicates the STN DBS reduces the activity of neurons in the basal ganglia output nucleus. However, it's not the real time observation of neuronal activity during DBS. In this study, the optical calcium imaging system will be implanted into the internal Globus Pallidus of MTPT injuried rhesus to investigate the calcium level and spiking of the neurons when high and low frequency stimulation are given out respectively. Additinally, the ECoG will be used to record the motor cortical potential to study the correlation of the electrical activity of motor cortex and the neuronal spiking of motor cortex. The results of study will uncover the mechanism of DBS concerning the neuron responses inside the basal ganglia- motor cortex network, which will bring out new ideas to the treatment of PD and other neurological and psychiatric diseases.

帕金森病（Parkinson's disease, PD）是最常见的神经退行性疾病之一，严重影响中老年人的身体健康。临床实践表明，脑深部电刺激（DBS）内侧苍白球或丘脑底核有效改善PD患者的运动功能。目前认为是因为调节基底节-运动皮层异常环路。但是DBS如何调节环路中的神经元活动并不明确，原因是DBS本身产生很强的电信号，用传统电极记录到的神经元放电信号因此受到干扰。课题组前期研究发现高频电刺激PD大鼠丘脑底核抑制基底节输出核团钙调蛋白的表达，表明基底节核团兴奋性下降，但由于不是对神经细胞活动的实时观察，结果存在一定局限性。本课题中，我们采用先进的深部钙成像技术，实时观察DBS MTPT致损PD猴内侧苍白球时，内侧苍白球和运动皮层神经元放电水平，同时用ECoG记录运动皮层电位。本研究将揭示DBS治疗PD对运动神经环路中神经元的影响，为DBS治疗PD及其他神经精神疾病提供新思路和新方法。

帕金森病（Parkinson’s disease, PD）是最常见的神经退行性疾病之一，严重影响中老年人的身体健康。临床实践表明，脑深部电刺激（DBS）内侧苍白球或丘脑底核有效改善PD 患者的运动功能。目前认为是因为调节基底节-运动皮层异常环路。然而，局灶性神经刺激引起的对直接和间接途径的全脑影响如何在个体患者中引起治疗效果尚不清楚。了解这一点对于推进基于神经回路的指导以优化候选患者筛查，术前目标选择和术后参数调整仍然至关重要。为了解决这个问题，我们提出了一种基于功能性脑连接的建模方法，该方法模拟刺激不同大脑区域的扩散效应，并量化计算机中异常网络拓扑的整流。我们通过精确定位基底神经节回路中的核团, 使用本地和来自公共数据库的帕金森病患者脑功能影像数据来验证这些分析。这些研究结果强调了神经网络模型在推进个性化脑刺激治疗方面的潜力，需要未来的实验研究验证其临床效用。