Metabolic state has a profound impact on cognitive function and our perception of the external world. However, the mechanisms underlying behavioral changes during the transition from mild to severe starvation are poorly understood. Here, we propose to take advantage of the anatomical simplicity and genetic tractability of Drosophila to study how shifts in metabolic state shape olfactory circuit function and thus impact appetitive olfactory behavior. There are remarkable similarities between Drosophila and mammals in the organization and molecular regulation of olfactory systems, suggesting shared principles in the neurobiology of hunger. Elucidating how changes in olfactory neural circuits impact the perception of food quality and dietary selections may lead to a better understanding of factors that contribute to obesity as well as anorexia in the infirm and elderly. The experiments outlined here investigate the hypotheses that the decline of insulin, a global satiety signal, triggers local neuropeptide signaling to recruit distinct neuronal populations at different stages of starvation. The goals of these experiments are: 1) investigating the temporal expression pattern of sNPF receptors in different neuronal populations; 2) investigating the role of local sNPF (a homolog of NPY in Drosophila) signaling in modulating neuronal excitability in a higher order olfactory center; 3) Investigate changes across the broader gamma lobe MBON network.

Public Health Relevance

Obesity is a seemingly unstoppable epidemic that affects a large population. The work of this proposal is basic science that seeks to reveal the connection between olfaction and appetitive behavior. Defining the olfactory circuits that modulate feeding behavior will create a knowledge base from which potential molecular targets can be evaluated for future therapeutic interventions.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Molecular Neurogenetics Study Section (MNG)
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Hyde, James F
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University of California San Diego
Schools of Arts and Sciences
La Jolla
United States
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Sethi, Sachin; Wang, Jing W (2017) A versatile genetic tool for post-translational control of gene expression in Drosophila melanogaster. Elife 6:
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Su, Chih-Ying; Wang, Jing W (2014) Modulation of neural circuits: how stimulus context shapes innate behavior in Drosophila. Curr Opin Neurobiol 29:9-16
Sen, Sonia; Cao, Deshou; Choudhary, Ramveer et al. (2014) Genetic transformation of structural and functional circuitry rewires the Drosophila brain. Elife 3:
Chihara, Takahiro; Kitabayashi, Aki; Morimoto, Michie et al. (2014) Caspase inhibition in select olfactory neurons restores innate attraction behavior in aged Drosophila. PLoS Genet 10:e1004437

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