Feeding state, insulin and NPR-1 modulate chemoreceptor gene expression via integration of sensory and circuit inputs.

Matthew Gruner,Alexander M Van Der Linden,Dru Nelson,Chrisopher V Gabel,Ari Winbush,Samuel H Chung,Leesun Ryu,Rebecca Hintz,Kyuhyung Kim,Kaveh Ashrafi

doi:10.1371/journal.pgen.1004707

Matthew Gruner, Alexander M Van Der Linden + Show 8 more

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https://doi.org/10.1371/journal.pgen.1004707

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Abstract

Feeding state and food availability can dramatically alter an animals' sensory response to chemicals in its environment. Dynamic changes in the expression of chemoreceptor genes may underlie some of these food and state-dependent changes in chemosensory behavior, but the mechanisms underlying these expression changes are unknown. Here, we identified a KIN-29 (SIK)-dependent chemoreceptor, srh-234, in C. elegans whose expression in the ADL sensory neuron type is regulated by integration of sensory and internal feeding state signals. We show that in addition to KIN-29, signaling is mediated by the DAF-2 insulin-like receptor, OCR-2 TRPV channel, and NPR-1 neuropeptide receptor. Cell-specific rescue experiments suggest that DAF-2 and OCR-2 act in ADL, while NPR-1 acts in the RMG interneurons. NPR-1-mediated regulation of srh-234 is dependent on gap-junctions, implying that circuit inputs regulate the expression of chemoreceptor genes in sensory neurons. Using physical and genetic manipulation of ADL neurons, we show that sensory inputs from food presence and ADL neural output regulate srh-234 expression. While KIN-29 and DAF-2 act primarily via the MEF-2 (MEF2) and DAF-16 (FOXO) transcription factors to regulate srh-234 expression in ADL neurons, OCR-2 and NPR-1 likely act via a calcium-dependent but MEF-2- and DAF-16-independent pathway. Together, our results suggest that sensory- and circuit-mediated regulation of chemoreceptor genes via multiple pathways may allow animals to precisely regulate and fine-tune their chemosensory responses as a function of internal and external conditions.

Highlights

An animals’ feeding state and food availability dramatically alters the responsiveness of chemosensory neurons and behavioral output to suit the needs of the animal to, for instance, locate food, find mates and avoid predators under different environmental conditions
We have developed an in vivo reporter assay in C. elegans for monitoring the expression of a candidate chemoreceptor gene in a single sensory neuron type, called ADL-specific sre-1 promoter (ADL), as a function of feeding state
We show that sensory inputs into ADL and neural outputs from ADL, as well as inputs from the RMG interneuron, which is electrically connected to ADL, are required to fine-tune expression of chemoreceptor genes in ADL

Summary

Introduction

An animals’ feeding state (i.e. fed versus starved) and food availability dramatically alters the responsiveness of chemosensory neurons and behavioral output to suit the needs of the animal to, for instance, locate food, find mates and avoid predators under different environmental conditions. These state-dependent changes in chemosensory behaviors have long been thought to arise from plasticity in central processes, there is growing evidence that feeding state gates responses in peripheral chemosensory neurons themselves, thereby directly modulating changes in chemosensory behaviors [1]. Dynamic changes in the expression levels of chemoreceptor genes may provide a simple mechanism by which chemosensory neurons may alter their responses to specific chemical stimuli under different feeding state conditions. Pre-exposure of C. elegans to salt in the absence of food switches the normally attractive salt response to avoidance, and this

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