The brain of an awake, mature human (and other mammals) consciously and subconsciously “knows” the body’s configuration in 3D space on a moment-by-moment basis. This is often referred to as the “body schema” representation in the brain. Body schema is critical for self- awareness and for motor control. For example, we can effortlessly use our hand to touch our nose or swat a mosquito that has just landed on the back of the neck, regardless of the starting positions of the hand, because we have an intimate knowledge of the body’s position in 3D space at any given moment. Yet how the brain generates body schema representation remains largely unknown. Here we propose to systematically examining the neural circuits and mechanisms that compute the 3D positions of all body segments (individually or combined) with egocentric reference frames in the mouse brain. This is achieved by (1) developing an algorithm, BodySchemeJ, that generates fully parameterized moment-to-moment description of full body configurations in freely moving mice; (2) performing large-scale multi-electrode array recordings from multiple brain areas with concurrent tracking of body configurations in free- moving behaviors; (3) computational analysis of neural data and testing the hierarchical body schema representation hypothesis; and (4) delineating the presynaptic inputs and output targets of identified body schema cells. Finally, since body schema representation deficits are observed in many neurological diseases, we will test how body schema is abnormally encoded in a mouse model of autism. The pioneering knowledge gained from this research will help to establish a new conceptual framework to advance our understandings of quintessential neurobiological processes such as self/body awareness, localizing sensations to body parts in 3D space, action selection and motor control.

Body schema, i.e the body’s configurations and positions in 3D space, is critical for self- awareness and for motor control. Yet how the brain generates and updates such representation remain largely unknown. This research will not only solve this fundamental neuroscience mystery, but also provide insights into body schema representation deficits observed in many neurological diseases.