Mathew Lab

Summary: An animal’s satiety state modulates smell neurons in the mammalian olfactory bulb (OB) and the insect antennal lobe (AL), the first smell processing centers. Here, first-order olfactory sensory neurons (OSNs) connect with second-order projection neurons and local interneurons. In the first smell processing centers of Drosophila larvae, adult flies, and mammals, including humans, insulin is the main modulatory hormone that mediates the satiety-dependent changes in neuronal function. The Mathew lab is focused on understanding the molecular mechanisms by which insulin mediates the hunger-dependent changes in the functions of olfactory neurons in this first smell processing center. The projects in our lab are centered around two main questions: 1) How does hunger affect an animal’s sensitivity to odors? (in other words, what is the mechanism by which insulin affects the functions of first-order olfactory sensory neurons) and 2) How does hunger affect an animal’s decision-making during navigation toward odors? (in other words, what is the mechanism by which insulin affects the functions of Keystone-LN (an inhibitory local neuron)). To address these questions, we take advantage of the Drosophila larva as a model system, which allows incisive genetic and molecular analyses of olfactory neurons and their functions.

1) How does hunger affect an animal’s sensitivity to odors? (Investigating the molecular mechanisms by which hunger affects the function of olfactory sensory neurons in the Drosophila larva)

Using the Drosophila melanogaster larva, we showed that insulin and leptin pathways interact within OSNs to affect their function. We also showed that manipulating these signaling pathways specifically in the OSNs impact the larva’s behavior toward odors, its feeding behavior, and its body weight. With the help of the genetic, molecular, and imaging tools we have developed in the lab, we have a unique opportunity to determine the molecular mechanisms downstream of insulin signaling in OSNs and investigate their relationship to animal physiology.

Publication: 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 (2020) Scientific Reports 10(1):3119. [Link]

2) How does hunger affect an animal’s decision-making during navigation toward odors? (A genetic and molecular analysis of olfactory decision-making in the Drosophila larva).

Using the Drosophila melanogaster larva, we demonstrated a critical role for Keystone-LN, an antennal lobe local neuron, during larval head-sweep behavior. Head sweeps are an important adaptive behavior in crawling insects. We showed that insulin signaling in this key local neuron likely mediates satiety-dependent flexibility in head-sweep behavior, shaping the larva’s navigation. We will build on this research so far to ask another set of interesting questions: 1) how is the insulin signaling mechanism in an inhibitory local neuron distinct from other neurons? 2) why is it essential to modulate an inhibitory component of a circuit to adjust behavioral decisions based on satiety states?

Publication: Odell SR, Clark D, Zito N, Jain R, Gong H, Warnock K, Carrion-Lopez R, Maixner C, Prieto-Godino L, Mathew D. “Internal state affects local neuron function in an early processing center to shape olfactory behavior in Drosophila larvae,” (2022) Scientific Reports 12 (1): 15767. [Link]