Neural mechanisms underlying the restructuring of olfactory representations in the Drosophila mushroom body

California Institute Of Technology, Pasadena CA

Investigators

Abstract

Project Summary/Abstract Understanding the axes that organize the large and diverse space of odor stimuli for efficient encoding and decoding is a core challenge in olfaction. In addition to their physicochemical properties and molecular features, an important property of odorants is how they are organized relative to one another in natural environments. We hypothesize that the statistics of odorant correlations in natural settings, shaped by conserved metabolic and biochemical pathways in behaviorally important odor sources, are important to extracting information about the identity and ethological value of the source. To understand how animal brains accomplish this task, we trace how odors are formatted and encoded at successive stages of neural processing in the olfactory system of the vinegar fly Drosophila melanogaster. We recently discovered that the fly olfactory code is unexpectedly restructured between primary olfactory receptor neurons (ORNs) at the periphery and the mushroom body (MB), a third-order associative olfactory processing region. Specifically, odor relationships encoded in the MB better reflect the relationships of monomolecular volatiles in behaviorally relevant natural sources, compared to their similarity with respect to chemical features, and the converse was true for odor relationships encoded in peripheral ORNs. The goal of this project is to understand the principles and neural mechanisms underlying this restructuring, guided by the hypothesis that this process reflects the progressive reformatting of the olfactory code to encode variables relevant to behavioral significance. To achieve this goal, Aim 1 will test the hypothesis that an important organizing principle for olfactory coding and behavior is the metabolic relationship between odorants, structured by conserved biochemical processes in natural odor sources; Aim 2 will systematically map the transformation of odor representations at each synaptic stage of olfactory processing, thereby elucidating the neural circuit mechanisms that underlie these transformations; and Aim 3 will determine how neural activity and olfactory experience contribute to the structure of olfactory codes in the MB. Our research plan describes how we will achieve these goals by leveraging the well-mapped connectivity of the fly nervous system, the ability to selectively measure and manipulate neural activity in defined neural populations, and the adaptation of geometric approaches, originally developed for understanding human visual perceptual spaces, as a computational framework for mapping how olfactory representational spaces are transformed along the fly olfactory pathway. This project will advance our understanding of the broad and important problem of how sensory systems capture natural stimulus structure and use it to progressively reorganize sensory representations into formats useful for making semantic inferences about objects in the natural world in relation to their behavioral needs.