Functional maturation of neural circuits for biological motion perception and social engagement

项目摘要/摘要 群居动物可以通过相互注视来获取信息--注意 组成员并相应地调整他们的操作。这在脊椎动物的行为中很明显，比如 灵长类和一些鱼群的种类，它们确定它们的位置、姿势和前进方向 根据他们的社会伴侣的位置、姿势和凝视。照顾到生物体的能力 他人的运动暗示也是人类社会发展的一个标志，并在幼儿时期就出现 通常是发育中的儿童。相比之下，患有自闭症谱系障碍(ASD)的儿童表现明显 他们注意到生物运动线索的能力缺陷--包括身体姿势和凝视方向--a 严重的社会损害，可能是幼儿自闭症的早期征兆。尽管它很重要，但 调节生物运动信息的功能和功能障碍处理的神经电路有 人们对此知之甚少，部分原因是研究分布在大脑皮层下的神经回路面临挑战 哺乳动物的发育。在这里，我提出了一种研究社交大脑发展的研究策略 鱼群中生物运动感知的回路，利用高度保守的皮质下 支持脊椎动物天生的视觉处理、定向行为和社会参与的网络。我的 实验室将研究脊椎动物微型玻璃鱼(Danion Ella Erebrum)的社会脑发育 具有遗传适应性、体积小、终身光学透明等特点的模型系统， 能够在成年期进行全脑的体内细胞分辨率钙成像。我们的初步数据显示 仅基于视觉的成人丹尼奥拉学派，允许对自然主义进行精确的实验控制 实验室里的社交刺激。通过利用这些独特的属性，我们建议在这里研究整个大脑 支持生物运动知觉发展的网络--及其在遗传上的功能障碍 ASD模型-使用一种新的组合，在整个发育过程中使用多动物姿势跟踪 集体行为、增强和虚拟现实(AR/VR)任务、全脑蜂窝级功能 成像，以及ASD相关基因的Crispr-Cas敲除。我的实验室将应用这种多学科的方法 为了确定生物运动处理和协调的群体行为的发展进程， 编码同种行为和驱动的视觉感知的多区域神经群体 适当的定向反应，以及发育中的神经回路和群体行为功能障碍 ASD的多种遗传模式。通过建立这一社会成熟的示范体系，并专注于 神经回路在脊椎动物中是保守的，我们的工作将促进快速发现全脑 与ASD典型和病理发育相关的功能模体。

Project Summary/Abstract Social animals can obtain information by looking at one another – paying attention to the “body language” of group members and adjusting their actions accordingly. This is evident in the behavior of vertebrates such as primates and some species of schooling fish, which orient their position, posture, and heading direction according to the position, posture, and gaze of their social partners. The ability to attend to the biological motion cues of others is also a hallmark of human social development, and emerges early in infancy for typically developing children. In contrast, children with Autism Spectrum Disorder (ASD) display pronounced deficits in their ability to attend to biological motion cues – including body posture and gaze direction – a critical social impairment that can be an early sign of ASD in young children. Despite its importance, the neural circuits mediating the functional and dysfunctional processing of biological motion information are poorly understood, in part due to the challenges of studying distributed subcortical circuits across development in mammals. Here I propose a research strategy to study the development of social brain circuits for biological motion perception in schooling fish, taking advantage of highly- conserved subcortical networks that support innate visual processing, orienting behavior, and social engagement in vertebrates. My lab will study the development of the social brain in the micro glassfish (Danionella cerebrum), a vertebrate model system with the unique features of genetic amenability, small size, and life-long optical transparency, enabling brain-wide in vivo cellular-resolution calcium imaging in adulthood. Our preliminary data indicate that adult Danionella school based on vision alone, which allows for precise experimental control over naturalistic social stimuli in the lab. By leveraging these unique attributes, here we propose to investigate the brain-wide networks that underlie the development of biological motion perception – and its dysfunction in genetic models of ASD – using a novel combination of multi-animal posture tracking across the development of collective behavior, Augmented and Virtual Reality (AR/VR) tasks, brain-wide cellular-level functional imaging, and Crispr-Cas knockout of ASD-associated genes. My lab will apply this multidisciplinary approach to identify the developmental progression of biological motion processing and coordinated group behavior, the multi-regional neural populations that encode the visual perception of conspecific actions and drive appropriate orienting responses, and the dysfunction of developing neural circuits and group behavior in multiple genetic models of ASD. By establishing this model system for social maturation and focusing on neural circuits that are conserved across vertebrates, our work will facilitate the rapid discovery of brain-wide functional motifs related to typical and pathological development in ASD.