Identifying, manipulating, and studying a complete sensory-to-motor model behavior circuit

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Project Summary How does the brain transform sensory information into complex behavior? The objective of this proposal is to identify the relevant neurons across the brain that are necessary to produce a relatively simple motivated behavior to study and identify fundamental principles underlying coding. Sensory-to-behavior circuits must contain a variety of neural computations such as those that determine the identity and meaning of the sensed cues, gauge internal state, remember previous experience, and command muscle action. However, without knowing all of the parts of a model circuit, studying where and how these computations occur has proven difficult. Currently, complete circuit structure underlying most behaviors is largely unknown, and no complete model circuit has been traversed through the mouse limbic system. Therefore, study of neural coding relies on investigation of single brain regions, such as subdivisions of the amygdala or hypothalamus. Such focus may be akin to blind men touching different parts of an elephant; without perceiving the entirety, interpretation may become distorted. Here we propose that sensation-to-motivated-behavior employs an entire circuit and its study as a whole will accelerate understanding. We will overcome this bottleneck by leveraging the systematic control of the mouse’s olfactory system to elicit urine-marking behavior as an ideal model circuit. Upon smelling females, male mice are motivated to intentionally deposit copious urine marks to advertise their sexual availability. To investigate how this motivated circuit encodes behavior, we will 1) identify a complete, sensory-to-muscle, anatomic circuit that generates behavior, 2) determine the activity patterns of the relevant neurons in relationship to the behavior and to each other, and 3) determine the neural logic across the circuit that integrates internal state and experience. Completion of these aims will provide a unified picture of how a simple motivated behavior is coded in the brain. We expect that it will also provide the experimental means to identify and assign order and structure of basic known and unexpected principles that underlie how information is represented, altered, and integrated as it journeys from initial olfactory sensation to ultimate muscle activity. Once completed, both the approach and resulting knowledge will provide solutions for us and others to use as a template for the mechanistic study of the logic of sensory-to-behavior across other more complex motivated circuits. We anticipate that full knowledge of the parts and activity patterns the complete circuit will provide a crucial first step to understanding of how sensory systems, the brain, and the body collectively generate behavior.