神经环路是大脑的基本功能单位，神经系统中的阵发性疾病和神经环路活动的异常有直接关系，而神经退行性疾病的发病早期，神经环路连接的变化是比行为学症状更早的病理表现。申请人长期从事交叉学科的工作，开发了记录神经活动的纳米技术和调控神经活动的新型光纤技术，并应用新技术阐明了视觉环路发育中的规律，发表 SCI论文11篇，其中包括Nature Neuroscience、Nano Letters和Biomaterials等第一或通讯作者论文，他引240余次，获耶鲁大学Brown-Coxe博士后学者基金支持。申请人计划依托交叉学科背景优势，结合光遗传学和双光子成像技术，组建用于神经环路功能成像的在体光学探头系统，并研究视觉环路的功能构成以及视神经炎小鼠模型下的环路异常。该系统可望能为描绘大脑神经环路的功能图谱和研究神经环路异常的相关疾病提供一个有效的实验系统。

Neural circuit is the basic functional unit of the brain that connects cellular-level and behavior studies. Episodic brain diseases often directly link to abnormal neural activities in the neural circuit, while changes in neural circuit connections emerge before clinical symptoms at early stage of degenerative brain diseases. The applicant has been working on interdisciplinary projects throughout these years. The applicant developed neural activity recording techniques using nanoparticle and optrode techniques for cell-type specific activity manipulation, publishing 11 peer-reviewed papers including first authored ones in Nature Neuroscience, Nano Letters and Biomaterials. We propose to develop endomicroscope imaging system based on optogenetics and two-photon imaging technologies. These systems can be used to study the function of visual circuit and changes in visual circuit in neuritis disease model. We hope to use the imaging system to reveal unknowns in neural circuits and associated behavior and brain diseases.

项目研究内容主要从新技术发展和视觉环路的发育和功能等两个方面开展。新技术发展方面，完成了三个交叉课题：纳米线恢复小鼠视觉、基于视皮层脑机接口的颜色伪装和多色红外光遗传刺激。视觉环路的发育和功能方面，完成了三个课题：时间预测行为的视皮层机制、视网膜到外膝体精确投射的发育机制以及先天性寨卡综合症中的愈后视觉缺陷。在三年内，我们共发表标注基金号的通讯作者论文6篇（Nature Communications 2018, Advanced Materials 2018, Cerebral Cortex 2017, eBiomedicine 2017, Protein and Cell 2017, Neuroscience Bulletin 2017），美国德州大学Pei-Yong Shi教授专门撰写了评论文章，介绍我们的工作。另有2篇论文准备投稿；申请专利3项，批准1项。