Dopamine receptors antagonistically regulate behavioral choice between conflicting alternatives in C. elegans.

Daoyong Wang,Yinxia Li,Dayong Wang,Yonglin Yu,Yang Wang,Denis Dupuy

doi:10.1371/journal.pone.0115985

Abstract

Caenorhabditis elegans is a useful model to study the neuronal or molecular basis for behavioral choice, a specific form of decision-making. Although it has been implied that both D1-like and D2-like dopamine receptors may contribute to the control of decision-making in mammals, the genetic interactions between D1-like and D2-like dopamine receptors in regulating decision-making are still largely unclear. In the present study, we investigated the molecular control of behavioral choice between conflicting alternatives (diacetyl and Cu2+) by D1-like and D2-like dopamine receptors and their possible genetic interactions with C. elegans as the assay system. In the behavioral choice assay system, mutation of dop-1 gene encoding D1-like dopamine receptor resulted in the enhanced tendency to cross the Cu2+ barrier compared with wild-type. In contrast, mutations of dop-2 or dop-3 gene encoding D2-like dopamine receptor caused the weak tendency to cross the Cu2+ barrier compared with wild-type. During the control of behavioral choice, DOP-3 antagonistically regulated the function of DOP-1. The behavioral choice phenotype of dop-2; dop-1dop-3 triple mutant further confirmed the possible antagonistic function of D2-like dopamine receptor on D1-like dopamine receptor in regulating behavioral choice. The genetic assays further demonstrate that DOP-3 might act through Gαo signaling pathway encoded by GOA-1 and EGL-10, and DOP-1 might act through Gαq signaling pathway encoded by EGL-30 and EAT-16 to regulate the behavioral choice. DOP-1 might function in cholinergic neurons to regulate the behavioral choice, whereas DOP-3 might function in GABAergic neurons, RIC, and SIA neurons to regulate the behavioral choice. In this study, we provide the genetic evidence to indicate the antagonistic relationship between D1-like dopamine receptor and D2-like dopamine receptor in regulating the decision-making of animals. Our data will be useful for understanding the complex functions of dopamine receptors in regulating decision-making in animals.

Highlights

Dopamine regulates a variety of behavioral activities in both vertebrates and invertebrates
We investigated the molecular control of behavioral choice by D1-like and D2-like dopamine receptors and their possible genetic interactions with C. elegans as the in vivo assay system
Different from the dop-1(vs100) mutant, index of dop-2(vs105) or dop-3(vs106) mutant was lower than that of wild-type animals when both Cu2+ ion and diacetyl were presented in the assay system (Fig. 2B and 2C), implying that the inhibition of diacetyl chemotaxis by Cu2+ ion may be stronger than the inhibition of Cu2+ avoidance by diacetyl in dop-2 and dop-3 mutants

Summary

Introduction

Dopamine regulates a variety of behavioral activities in both vertebrates and invertebrates. Dopamine can act through five receptors that are grouped into several classes. D1-like and D2-like dopamine receptors usually have antagonistic effects on behaviors in mammals [1]. In Caenorhabditis elegans, there are four dopamine receptors: DOP-1, DOP-2, DOP-3, and DOP-4 [2]. DOP-2 and DOP-3 are D2-like dopamine receptors. DOP-4 is unique in invertebrate and distinct from mammalian D1-like dopamine receptors [3]. Previous study has demonstrated that DOP-1 and DOP-3 had antagonistic effects on basal slowing response in C. elegans [2]. DOP-1 and DOP-3 could further activate antagonistic Gaq and Gao signaling pathways to regulate the basal slowing response [2]

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Results

Conclusion