A Brain Circuit Program for Understanding the Sensorimotor Basis of Behavior Abstract The Project team's long-term goal is to develop a comprehensive theory of animal behavior that explicitly incorporates neural processes operating across hierarchical levels — from circuits that regulate the action of individual muscles to those that regulate behavioral sequences and decisions. Our innovative approach is guided by the notion that different brain regions are not linked within a single neuroanatomical tier, but rather constitute a series of hierarchically nested feedback loops. The effort is organized into four Research Projects, each focusing on a different processing stage related to: (1) muscle action, (2) motor patterns, (3) motion guidance, and (4) behavioral sequences. Demonstrating our commitment to team interaction, these Research Projects are not organized according to PIs laboratories, but rather each constitutes a collaborative multi- laboratory effort. The collective expertise of our research team spans the entire nervous system - from the sensory periphery to the motor periphery and was chosen to include experts in every experimental technique we require (molecular genetics, electrophysiology, optical imaging, biomechanics, quantitative behavioral analysis, control theory, and dynamic network theory). We will exploit mathematical approaches – control theory and dynamic network theory in particular – that are best suited to model feedback and the flow of information through and among different processing stages in the brain. The four complimentary and integrated Research Projects will focus on ethologically relevant natural behaviors, with an emphasis on recording methods that interrogate the functions of genetically identified neurons in intact, behaving animals – a rigorous standard that is designed to have the broadest impact on systems neuroscience. Our research exploits a single, experimentally tractable model system (Drosophila melanogaster), in which we can easily study the functions of genetically identified cell classes in ethologically relevant behaviors. Our experiments emphasize methods that interrogate the functions of neurons in intact, behaving animals, a rigorous standard that is designed to have the broadest impact on systems neuroscience. Our research will be supported by an Instrumentation and Software Resource Core that will develop and support novel devices and software, so that we can continue to employ state-of-the-art experimental techniques and data analysis. Collectively, our research program constitutes a systematic attack on the neural basis of behavior that integrates vertically across phenomenological tiers. The result of our effort will be a new synthesis of how a fully embodied brain works to generate behavior.

Project Narrative Our studies should lead to a more integrative understanding of why so many different brain regions in the brain and spinal cord are mutually interconnected, creating a dense network of "two-way streets" whereby sensation guides motor control, but motor plans and actions also filter and focus our sensory experiences. These issues are fundamental to developing better ways to diagnose and treat a wide range of conditions, including pain syndromes, movement disorders (Parkinson's disease, stroke, spinal cord injury), and even cognitive disorders that impair attention and executive control (attention-deficit/hyperactivity disorder, schizophrenia). Finally, the results of our studies should contribute to the development of better prosthetic devices and assistive robots that can recapitulate features of the brain's normal interface between sense organs and motor control circuitry.