Main Research Focus (OSN Modulation)

Starved-State Dependent Modulation of Olfactory Sensory Neurons in Drosophila Larvae.

Starvation increases olfactory sensitivity that encourage animals to search for food. This has been shown in insects, worms, and mammals including humans. Olfaction researchers will acknowledge that while studies in the last several decades have greatly improved our understanding of how odors are received and processed by sensory neurons, the mechanisms that enable sensory neurons to remain flexible and adapt to the animal’s starved state are poorly understood. Additionally, breakdown in these modulatory mechanisms lead to abnormal food-search behavior and feeding habits in animals, which in turn lead to disease states such as obesity. Obesity researchers will readily acknowledge that while several obvious risk factors for obesity such as genetics, nutrition, metabolism, and environment have been heavily researched, the relationship between nutrient sensing and obesity remains grossly understudied.

OSN-modulationThe current mechanistic model of state-dependent modulation of olfactory sensory neurons (OSN) is incomplete and several questions remain. Recently, we have shown that starved state enhances food-search behavior in the Drosophila larva. This modulation depends on both insulin and GABA signaling in OSNs. Insulin and GABA signaling interact within OSNs. Manipulating their levels in OSNs reduced the larva’s starvation-dependent increase in attraction toward odors and led to increases in its body-weight. The current work builds upon this framework. It leverages a wide array of innovative approaches, several of which were developed in our lab, to address highly significant questions regarding starved-state modulation of OSN function and its impact on foraging and feeding behaviors, as well as on weight-gain in the larva. We want to determine how the insulin/GABA signaling pathway effects changes in OSN function and food-search behavior. We also want to explore the relationship between OSN modulation and changes in the animal’s body weight. The results of these studies will help explain how an animal’s starved state modulates OSN function and how disorders in the pathway lead to disease states like obesity.

Significance of this Research: First, the mechanisms driving these neural circuit modulations are fundamental to our understanding of how neural circuits support animal cognition and behavior. If we better understood these mechanisms, we could learn how flexibility and the ability to adapt to a particular internal state are built into the sensory circuit. Second, understanding the mechanisms by which the starved state of an animal modulates its olfactory sensitivity and thereby controls its foraging behavior is important for both olfactory and appetite research. Third, we cannot ignore these questions in light of the obesity epidemic and the demonstration that obese adults have reduced olfactory sensitivity.

Publications:

Slankster E, Kollala S, Baria D, Dailey-Krempel B, Jain R, Odell SR and Mathew D. Mechanism underlying Starvation-dependent modulation of olfactory behavior in Drosophila larva. Elife (under review).