基因治疗运动神经元疾病Gene therapy for motor neuron disease
运动神经元疾病是一类以运动神经元选择性、进行性退化为特征的神经退行性障碍疾病。在该类疾病中，肌萎缩侧索硬化和脊髓型肌萎缩分别在成人和儿童中最为常见。过去数十年研究已使我们对这种危害极大疾病的病理有了越来越多的了解，但迄今为止还没有根治的方法。近年的研究显示出基因治疗在该病治疗中的巨大开发潜力，研究的重点是如何选择治疗性基因导入载体和导入路径并把两者进行有机结合。我们实验室的研究方向之一就是，利用新型病毒载体以优化的外周导入方式开发安全、高效的运动神经元疾病的基因治疗方案。
Motor neuron diseases (MNDs) are a group of neurodegenerative disorders characterized by the selective and progressive degeneration of motoneurons. Amongst MNDs, amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) are the most common in adults and children, respectively. Past decades of research have provided extensive insights into the pathophysiology of these devastating diseases, but, to date, no cure exists for them. Gene therapy represents a promising approach for treatment of MNDs. The main focus is on the right combination of vector and route of delivery, which is critical for MNDs gene therapy. The aim of our study is to find a safe and efficient scheme for MNDs gene therapy with optimized strategy of peripheral delivery using novel virus vector.
自主行动的神经原理Neural mechanisms of voluntary movements
自主行动是机体通过行动对思想的一种表达过程，包括行动计划和行动执行。自主行动对于动物体的生存至关重要。然而我们对自主行动神经生物学基础的了解还很肤浅。在我们实验室的研究中，我们正利用双光子显微镜技术和小显微镜技术对自由活动动物的神经网络可塑性进行成像，同时我们还结合应用神经环路追踪、光遗传和化学遗传等多项技术，力图回答以下问题：（1）介导自主行动不同步骤时，各关键环路的活动如何精密编排和协调；（2）参与调控自主行动的关键环路之间的功能连接原理；（3）介导自主行动不同步骤的关键环路在各时空节段的功能可塑性和结构可塑性变化规律。我们希望能够为解析自主行动的中枢神经环路再构建原理提供关键信息。
Voluntary movements are the expression of thought through action and contain planning and execution components. These movements are crucial for the survival of a species. Our understanding of the neural substrates underlying the voluntary movements is still lacking. In our study, by imaging the neuronal plasticity in freely behavial animals using two photon/miniscope and combining with circuit tracing, opto-genetics and chemical-genetics, we will address: (1) the parallel-ordered circuits to orchestrate multistep voluntary movements ; (2) the functional connections of main regions in multistep voluntary movements; (3) the functional and structural plasticity across different spatial and temporal scales that mediate different step of voluntary movements. Our work will provide crucial information on plausible neuronal substrates contributing to brain reorganization underlying voluntary movements.
