The Circuit Logic of Modulation of Locomotion by Odors

Drexel University, Philadelphia PA

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Abstract

PROJECT SUMMARY There is a fundamental gap in our understanding of the circuit mechanisms underlying even simple naturalistic behaviors, such as making a cup of coffee, which proceed through a sequential execution of sub-behaviors. The continued existence of this gap represents an important problem because obtaining a circuit-level understanding of complex multi-step behaviors is a necessary step toward unlocking the mysteries of healthy brain function and disorders. The overarching goal is to obtain a circuit-level understanding of such naturalistic behavior. The research objective here is to unravel the logic of sensorimotor transformation in the context of odor modulation of locomotion in Drosophila. Our group has pioneered methods to quantitatively assess how odors affect a fly's locomotion. We have also described the overall transformation between the activity of the olfactory receptor neurons (ORNs) and the resulting change in locomotion and found that this transformation is well-described by a mapping between the activity in the ORN and changes in locomotor parameters. This mapping is distinct for different locomotor parameters and suggests that there are parallel sensorimotor modules. The central hypothesis underlying the research proposed here is that the third-order olfactory neurons in the fly's lateral horn (LH) play an important role in mediating this transformation. LH receives input from the fly's olfactory system and is connected to premotor neurons in the fly's brain, and is, therefore, in the correct anatomical location to transform activity in the olfactory system into changes in locomotion. In particular, we hypothesize that lateral horn output neurons (LHONs) will mediate the specific transformation between ORN activation and each locomotion parameter. This hypothesis was formulated based on previous work and preliminary data. The rationale for the proposed research is that understanding odor-guided locomotion—a complex, flexible behavior—in the context of a genetically tractable system will allow a precise delineation of the steps that underlie sensorimotor transformation in the context of naturalistic behavior. The hypothesis above will be tested by characterizing the circuit basis of modulation of locomotion by food odors using a combination of techniques, including imaging, electrophysiology, quantitative behavior, and computation. The proposed research has three specific aims. 1) To investigate the rules of olfactory sensory integration in the context of naturalistic behaviors 2) To investigate the relationship between activity in LHONs and locomotion. 3) To investigate the contribution of LHONs in different contexts. The research is innovative because it employs sophisticated statistical tools and cutting-edge experimental tools in the context of a genetically tractable model organism to obtain insights into naturalistic behaviors. The proposed research is significant because it will vertically advance our understanding of sensorimotor processes involved in naturalistic behaviors. Besides representing a vertical advance in our understanding of naturalistic behavior, another possible positive outcome of this study is a better diagnosis of neurological conditioning that occurs through improper sequencing of actions.