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

生物运动感知和社会参与的神经回路的功能成熟

• 批准号: 10687450
• 负责人: Matthew Lovett-Barron
• 金额: $ 137.87万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-30 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10687450
• 关键词: Adult; Animals; Attention; Augmented Reality; Behavior; Behavioral; Biological; Biological Models; Brain; Brain region; Calcium; Cerebrum; Child; Cues; Data; Development; Fishes; Functional Imaging; Functional disorder; Genes; Genetic; Genetic Models; Human; Image; Impairment; Knock-out; Mammals; Measures; Mediating; Motion; Motion Perception; Optics; Pathologic; Population; Population Dynamics; Positioning Attribute; Posture; Primates; Research; Resolution; Schools; Social Development; Stimulus; Symptoms; Vertebrates; Vision; Visual Perception; Visual attention; Visual impairment; Work; autism spectrum disorder; autistic children; biological development; body language; experience; gaze; in vivo; infancy; interdisciplinary approach; member; neural; neural circuit; novel; response; social; social engagement; support network; virtual reality; visual processing

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.

项目概要/摘要 社会性动物可以通过互相注视来获取信息——注意对方的“肢体语言” 小组成员并相应地调整他们的行动。这在脊椎动物的行为中很明显，例如 灵长类动物和某些鱼群，它们可以确定自己的位置、姿势和前进方向 根据他们的社交伙伴的位置、姿势和目光。关注生物的能力 他人的动作线索也是人类社会发展的标志，并且在婴儿期早期就出现了 通常是发育中的儿童。相比之下，患有自闭症谱系障碍 (ASD) 的儿童表现出明显的 他们关注生物运动线索的能力存在缺陷——包括身体姿势和注视方向—— 严重的社交障碍可能是幼儿自闭症谱系障碍的早期征兆。尽管其重要性， 介导生物运动信息的功能性和功能失调处理的神经回路是 人们对此知之甚少，部分原因是研究分布式皮层下电路面临的挑战 哺乳动物的发育。在这里我提出一个研究社交大脑发育的研究策略 利用高度保守的皮层下神经元，研究鱼群生物运动感知的电路 支持脊椎动物先天视觉处理、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（Danionella cerebrum）的社交大脑的发育 模型系统具有遗传适应性、小尺寸和终生光学透明度的独特特征， 实现成年期全脑体内细胞分辨率钙成像。我们的初步数据表明 仅基于视觉的成人 Danionella 学校，可以对自然主义进行精确的实验控制 实验室中的社交刺激。通过利用这些独特的属性，我们建议研究全脑 生物运动感知发展背后的网络及其遗传功能障碍 ASD 模型——在整个发展过程中使用多动物姿势跟踪的新颖组合 集体行为、增强和虚拟现实 (AR/VR) 任务、全脑细胞水平功能 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方法 确定生物运动处理和协调群体行为的发展进程， 编码同种行为和驱动力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的功能障碍 ASD 的多种遗传模型。通过建立这个社会成熟模型系统并关注 脊椎动物中保守的神经回路，我们的工作将促进全脑的快速发现 与 ASD 的典型和病理发展相关的功能基序。