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

点击翻译按钮获取中文摘要

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.