大脑视觉皮层单个兴奋性神经元起始的神经网络结构和生理病理功能

人类大脑包含有数百亿个神经元，它们通过数千万亿个突触连接形成复杂而精密的神经环路网络，其负责几乎所有的感觉和认知行为。尽管近几年对大脑神经环路网络的研究不断发展，我们缺乏在高分辨率单细胞水平上对单个神经元起始的环路网络的深入认识。研究单个神经元起始的突触前和突触后神经网络的结构和功能，有助于我们在相对简单且分辨率极高的模型中认识大脑功能性网络活动特性、工作原理和形成机制，以及神经系统疾病可能的神经网络机制，具有很重要的生理病理学意义。.本课题拟使用病毒介导的环路示踪方法，标记视皮层单个兴奋性神经元的突触前和突触后神经网络，离体采用免疫组织化学和多通道全细胞记录研究其结构和突触连接特性；在体结合运用双光子钙成像、行为学、化学遗传学和光遗传学等实验方法，阐明这一神经网络的活动特性；最后通过构建抑郁症模型小鼠，揭示这一神经网络功能异常与抑郁症过滤非相关视觉信息功能障碍的潜在关系。

The human brain is composed of tens of billions of neurons; these neurons connect with each other through trillions of synapses to form enormously complex but incredibly precise neuronal networks, which are believed to be the structural basis for perception and behavior. Although neural networks have been being extensively studied in recent years, the single neurons-initiated neural networks are poorly explored, especially at high-resolution single cell level. Single neurons-initiated neural networks are an ideally simple and high-resolution platform to study the structure and function of neural networks, as well as their possible roles in psychiatric diseases..In this project, we plan to use virus-mediated neural circuit tracing techniques to label single excitatory pyramidal neurons-initiated presynaptic and postsynaptic neural networks; we will study the structural features and synaptic connections of these single cells-initiated neural networks in vitro using immunohistochemistry and multiple-channel whole cell recording. Besides, we will explore how these single cells-initiated neural networks are developed at early development stage, and to unveil the importance of sensory input for their formation. Furthermore, we will explore the functional perspectives of these neural networks in vivo using two-photon calcium imaging, behavioral paradigms, chemogenetics and optogenetics manipulation. Finally, we will study some potential dysfunctions in these neural networks in depression-related abnormality of filtering irrelevant visual information. We believe this study will provide us unprecedented evidences to showcase how the brain networks are structurally and functionally organized and developed, as well as how they function in perceptual behaviors and some psychiatric diseases.