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.

Public Health Relevance

Whether you smell delicious food or see a scary spider, scientists don?t know how sensory stimuli motivates behavior. The proposed research is relevant to public health because it will identify the connections and activity patterns of the whole program order to study how the brain converts sensation into voluntary action. Completion will enable us and others to begin to solve normal and dysfunctional behavior.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS108439-02
Application #
9789709
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
David, Karen Kate
Project Start
2018-09-30
Project End
2023-07-31
Budget Start
2019-08-01
Budget End
2020-07-31
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037