The modulation of behavior by basic physiological need is essential for animal survival. Relevant sensory stimuli are transformed by peripheral receptors into electrical signals to form an internal representation of the external world. Shaping sensory representation by internal physiological state of the organism could be an important mechanism to provide behavioral flexibility. In particular, hunger modulates feeding behavior in most animals to maintain energy homeostasis. Despite that olfaction makes important contribution to the perception of food quality, very little is known about how starvation alters olfactory representation. This proposal focuses on studying the hunger modulation in early olfactory processing. The proposed experiments will be carried out in Drosophila, an organism with an anatomically simple olfactory system that is amenable to molecular and genetic manipulations, optical imaging technologies, and behavioral analysis. The experiments outlined here investigate the hypotheses that insulin is a global satiety signal in the early olfactory system, and that both insulin and local neuropeptide signaling are integrated at specific sensory neurons to enable hunger modulation of olfactory sensitivity. The goals of these experiments are: 1) evaluating the hypothesis that insulin is a global metabolic signal for hunger modulation;2) investigating the role of local sNPF (a homolog of NPY in Drosophila) signaling in starvation-dependent presynaptic facilitation;3) investigating the role of local tachykinin signaling in starvation-dependent presynaptic inhibition. There is good evidence to suggest that this kind of hunger modulation in peripheral olfactory system is present in vertebrate systems. The notion that hunger modulation at the peripheral olfactory system is linked to insulin signaling has potential implication for therapeutic intervention of the seemingly unstoppable obesity epidemic trend in a large percentage of the population.

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 circuit 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
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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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