Functional and Molecular Dissection of Marmoset Face Areas

PROJECT SUMMARY Face perception is supported by multiple highly specialized regions, interconnected to form a face-processing network. Because of the clarity of its functional organization, the system has allowed for unprecedented insights into the neural mechanisms and computational principles of high-level object recognition at large. These insights were gained through recordings from face areas that have been blind to the molecular properties of face cells. Yet the conserved organization of face areas among primates suggest an evolutionary origin in which genetic alterations may have contributed to circuit-specific innovations in neuronal properties that endowed these areas with their function. Genes expression patterns differentiate one cortical area or cell type from another. Understanding the neuronal circuits that underly face processing requires relating the genetic identity of different face areas and individual face cells to their specific functions. In this project, we propose pilot work to generate a first-ever, cell-type-specific, functional map of face areas in the primate brain. We will use the common marmoset, a New World primate model amenable to genetic manipulation and with a lissencephalic brain accessible for optical imaging. We will leverage newly generated atlases of molecular-defined cell types of the marmoset brain that will guide the selection of gene panels to survey face areas. We have established methods that combine functional imaging with post-hoc spatial transcriptomics that allows for dense surveys of population activity and their subsequent cell-type identification. In Aim 1, we will combine optical intrinsic imaging with sequencing-based spatial transcriptomics to determine whether the topological arrangement of face patches can be defined by its molecular architecture. In Aim 2, we will combine population two-photon calcium imaging with imaging-based spatial transcriptomics to determine whether face-selective cells are defined by specific molecular cell types. This pilot study will lay the groundwork for the genetic dissection of cortical circuits underlying primate face processing. This will allow us to unravel the circuit-level computations that give rise to facial perception and how such processes are altered in neurodevelopmental and neurodegenerative disorders that disrupt social cognition.