PROJECT SUMMARY/ABSTRACT There is a fundamental gap in understanding the neural bases of social cognition. Atypical behaviors associated with mental disorders like autism spectrum disorders or major depressive disorder often present with deficits in social interaction. Understanding these deficits and developing targeted therapies will continue to prove impossible until the neural bases of typical social cognition are understood. To reveal these neural bases, it is the central thesis of this proposal to focus on those components of social cognition that allow precise external stimulus manipulation to elucidate social information processing. Faces form just such a category of uniquely social stimuli that bridge vision and social cognition. More so, faces are processed by a highly organized system of cortical areas that are tightly interconnected into a face-processing network. Still, past work on face patches has been critically limited to the properties of single face cells. In order to overcome these limitations, the common marmoset was recently discovered to have superficially located face patches, which, when paired with functional two-photon calcium imaging, enables simultaneous recordings from large populations of face cells. The long-term goal is to establish a mechanistic understanding of social cognition. The objective is to elucidate how a class of socially relevant stimuli is encoded by neural population in a cell-type dependent manner. The central hypothesis is that a face patch contains a map that exclusively represents faces in a spatially organized and cell-type specific manner. The rationale of this proposal is that it will establish the neural representation of faces, a basic component of social cognition, from the level of single cells to cortical maps in a new model system amenable to modern gene-editing approaches and thus disease model development. The hypothesis will be tested by pursing three specific aims: 1) to determine the functional specificity of a face patch; 2) to identify the principles of spatial organization within a face patch; and 3) to elucidate cell-type specific contributions to face processing. Under the first and second aim, two-photon microscopy will be used to measure neural activity from a large population of neurons. This will allow the determination of the spatial organization of face representations. Under the third aim, this technique will be combined with tissue clearing and volumetric immunohistochemistry to contribute morphological and cell type specific information about the population of neurons. The approach of this proposal is innovative because it combines several cutting-edge techniques with a novel model system to establish the functional architecture of a key social brain circuit. This research is significant because it generates a mechanistic understanding of face processing, illuminates a critical link between the visual system and the social brain, and forms a new model system in which further hypotheses underlying mechanisms of mental disorders can be rigorously tested to gain mechanistic understanding of a system tangibly contributing to our understanding of typical and atypical human behavior.

PROJECT NARRATIVE The ability to perceive a stimulus, recognize it as a socially relevant object, and transform this into an appropriate response is critical to complex social behavior, and often, this process is disrupted in psychiatric diseases including autism spectrum disorder or major depressive disorder. Our research is aimed at understanding the neural bases of social perception that enable primates to respond to faces as unique social stimuli. Our work would provide fundamental insight into how typical neural populations are functionally organized, and importantly, create a model in which it is possible to test how specific mechanisms of psychiatric diseases give rise to atypical social behavior.