Abstract

Starvation enhances olfactory sensitivity that encourage animals to search for food. The molecular mechanisms that enable sensory neurons to remain flexible and adapt to a particular internal state remain poorly understood. Here, we study the roles of GABA and insulin signaling in starvation-dependent modulation of olfactory sensory neuron (OSN) function in the Drosophila larva. We show that GABAB-receptor and insulin-receptor play important roles during OSN modulation. Using an OSN-specific gene expression analysis, we explore downstream targets of insulin signaling in OSNs. Our results suggest that insulin and GABA signaling pathways interact within OSNs and modulate OSN function by impacting olfactory information processing. We further show that manipulating these signaling pathways specifically in the OSNs impact larval feeding behavior and its body weight. These results challenge the prevailing model of OSN modulation and highlight opportunities to better understand OSN modulation mechanisms and their relationship to animal physiology.

Highlights

  • Starvation enhances olfactory sensitivity that encourage animals to search for food

  • The model does not account for interactions between GABA and insulin signaling pathways that are known to impact neuromodulation in both fly and mammalian systems: For instance, GABAB-Receptor (GABABR) mediates a GABA signal from fly brain interneurons, which may be involved in the inhibitory control of Drosophila insulin like peptide (DILP) production[17]; In mammalian CNS neurons, insulin increases the expression of GABAAR on the postsynaptic and dendritic membranes[15,18]; GABA administration to humans resulted in a significant increase in circulating Insulin levels under both fasting and fed conditions[18,19]

  • Using a novel olfactory sensory neuron (OSN)-specific gene expression analysis, we show that insulin and GABA signaling pathways interact within OSNs and modulate OSN function by impacting odor reception, olfactory information processing, and neurotransmission

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Summary

Introduction

Starvation enhances olfactory sensitivity that encourage animals to search for food. The molecular mechanisms that enable sensory neurons to remain flexible and adapt to a particular internal state remain poorly understood. We study the roles of GABA and insulin signaling in starvationdependent modulation of olfactory sensory neuron (OSN) function in the Drosophila larva. We further show that manipulating these signaling pathways in the OSNs impact larval feeding behavior and its body weight These results challenge the prevailing model of OSN modulation and highlight opportunities to better understand OSN modulation mechanisms and their relationship to animal physiology. The mechanisms by which an animal’s starved state modulates sensory neuron function remain poorly understood. The model does not account for the ultimate targets of insulin/GABA/sNPF signaling that alter OSN sensitivity to odors and its function. Understanding the mechanisms by which the starved state of an animal modulates its olfactory sensitivity and thereby controls its food-search behavior is important for both olfactory and appetite research.

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