RRC ID 4222
Author Dittman JS, Kaplan JM.
Title Behavioral impact of neurotransmitter-activated G-protein-coupled receptors: muscarinic and GABAB receptors regulate Caenorhabditis elegans locomotion.
Journal J. Neurosci.
Abstract Neurotransmitter released from presynaptic terminals activates both ligand-gated ion channels (ionotropic receptors) and a variety of G-protein-coupled receptors (GPCRs). These neurotransmitter receptors are expressed on both presynaptic and postsynaptic cells. Thus, each neurotransmitter acts on multiple receptor classes, generating a large repertoire of physiological responses. The impact of many ionotropic receptors on neuronal activity and behavior has been clearly elucidated; however, much less is known about how neurotransmitter-gated GPCRs regulate neurons and circuits. In Caenorhabditis elegans, both acetylcholine (ACh) and GABA are released in the nerve cord and mediate fast neuromuscular excitation and inhibition during locomotion. Here we identify a muscarinic receptor (GAR-2) and the GABA(B) receptor dimer (GBB-1/2) that detect synaptically released ACh and GABA, respectively. Both GAR-2 and GBB-1/2 inhibited cholinergic motor neurons when ACh and GABA levels were enhanced. Loss of either GPCR resulted in movement defects, suggesting that these receptors are activated during locomotion. When the negative feedback provided by GAR-2 was replaced with positive feedback, animals became highly sensitive to ACh levels and locomotion was severely impaired. Thus, conserved GPCRs act in the nematode motor circuit to provide negative feedback and to regulate locomotory behaviors that underlie navigation.
Volume 28(28)
Pages 7104-12
Published 2008-7-9
DOI 10.1523/JNEUROSCI.0378-08.2008
PII 28/28/7104
PMID 18614679
PMC PMC2679701
MeSH Acetylcholine / metabolism* Aldicarb / pharmacology Animals Animals, Genetically Modified Antinematodal Agents / pharmacology Behavior, Animal / physiology Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics Cholinesterase Inhibitors / pharmacology Gene Expression Regulation / drug effects Gene Expression Regulation / physiology Levamisole / pharmacology Locomotion / physiology* Luminescent Proteins / genetics Luminescent Proteins / metabolism Mutation Neurons / drug effects Receptors, Cholinergic / physiology* Receptors, GABA-B / physiology* gamma-Aminobutyric Acid / metabolism*
IF 6.074
Times Cited 36
C.elegans tm1406 tm1165