Stimulus valuation is a critical step in determining how we relate with the world. Yet the way the brain computes and represents value remains a matter of much debate. The assessment of potential food sources provides an expedient framework to address value representation in the brain given its ubiquity in nature. Moreover, with the global population facing overwhelming rises in the prevalence of obesity and obesity-related serious medical conditions, the need for understanding the processes governing food selection and preferences has become of paramount importance to human health. Under normal conditions most animals, including Drosophila, are extremely discerning about what food sources to approach, even when given the choice between multiple viable options and odors are one of the most important sensory cues all animals use to track, evaluate and select among available foods. How does the brain represent complex stimuli, in this case odorants, in order to generate appropriate behaviors to environmental cues? Drosophila are an unparalleled model organism with which to study such questions given their complex behavior, relatively tractable nervous system, and the wealth of genetic tools available to both observe and manipulate targeted neural populations. We will first establish Drosophila's partiality for differing food odrs behaviorally. We will then examine with single-cell resolution, using in vivo two-photon calcium imaging, the relationship between observed food- odor values and activity in targeted subsets of olfactory and neuromodulatory neural populations. We are specifically interested in the role of Drosophila Neuropeptide F neurons, the functional homolog of mammalian orexigenic Neuropeptide Y which is a prominent regulator of food-related appetitive behaviors. We will then genetically manipulate neural activity in these populations, both chronically and acutely, to alter behavioral preferences, establishing necessity and sufficiency. Once critical neural subsets are established we will map the connectivity of these neurons using a combination of photoactivation and immunostaining and then determine the functional characteristics of downstream targets through both genetic manipulation and functional imaging. Taken together, these experiments aim to describe how value of a specific class of stimuli, food odor, is flexibly represented in the brain and delineate a neural circuit for such flexible behavior. Our proposal to identify the manner and circuits by which the central brain computes food-odor value will not only inform our understanding of how the brain organizes incoming food-related information but ultimately how the brain translates sensory input into behavioral responses.
Obesity and obesity-related illness is fast becoming the major public health crisis facing the people and health infrastructure of the United States. Odor remains the single most valuable environmental cue that allows us to evaluate and select among possible food sources yet our basic understanding of how the value associated with differing odors is coded in the brain and relatedly whether food odors, with their unique place in food-seeking behavior, get special neural treatment, is at present absent. We aim to determine where and how food odor value is determined in the brain.
|Dubnau, Josh (2018) The Retrotransposon storm and the dangers of a Collyer's genome. Curr Opin Genet Dev 49:95-105|
|Beshel, Jennifer; Dubnau, Josh; Zhong, Yi (2017) A Leptin Analog Locally Produced in the Brain Acts via a Conserved Neural Circuit to Modulate Obesity-Linked Behaviors in Drosophila. Cell Metab 25:208-217|
|Sachse, Silke; Beshel, Jennifer (2016) The good, the bad, and the hungry: how the central brain codes odor valence to facilitate food approach in Drosophila. Curr Opin Neurobiol 40:53-58|
|Shuai, Yichun; Hirokawa, Areekul; Ai, Yulian et al. (2015) Dissecting neural pathways for forgetting in Drosophila olfactory aversive memory. Proc Natl Acad Sci U S A 112:E6663-72|