Abstract
Maps of the synapses made and neurotransmitters released by all neurons in model systems such as C. elegans have left still unresolved how neural circuits integrate and respond to neurotransmitter signals. Using the egg-laying circuit of C. elegans as a model, we mapped which cells express each of the 26 neurotransmitter G protein coupled receptors (GPCRs) of this organism and also genetically analyzed the functions of all 26 GPCRs. We found that individual neurons express many distinct receptors, epithelial cells often express neurotransmitter receptors, and receptors are often positioned to receive extrasynaptic signals. Receptor knockouts reveal few egg-laying defects under standard lab conditions, suggesting the receptors function redundantly or regulate egg-laying only in specific conditions; however, increasing receptor signaling through overexpression more efficiently reveals receptor functions. This map of neurotransmitter GPCR expression and function in the egg-laying circuit provides a model for understanding GPCR signaling in other neural circuits.
SIGNIFICANCE STATEMENT
Neurotransmitters signal through G protein coupled receptors (GPCRs) to modulate activity of neurons, and changes in such signaling can underlie conditions such as depression and Parkinson’s disease. To determine how neurotransmitter GPCRs together help regulate function of a neural circuit, we analyzed the simple egg-laying circuit in the model organism C. elegans. We identified all the cells that express every neurotransmitter GPCR and genetically analyzed how each GPCR affects the behavior the circuit produces. We found that many neurotransmitter GPCRs are expressed in each neuron, that neurons also appear to use these receptors to communicate with other cell types, and that GPCRs appear to often act redundantly or only under specific conditions to regulate circuit function.
Footnotes
The authors declare no competing interests.
We thank Eviatar Yemini and Oliver Hobert for the mgl-2(7.9kb)::gfp plasmid, and Kevin Collins and Helge Groβhans for the ida-1::mCherry and ajm-1::mCherry transgenes, respectively, and Steve Flavell for the outcrossed dop-4(ok1321) strain. Strains were provided by the C. elegans National BioResource Project of Japan and by the CGC, funded by the NIH Office of Research Infrastructure Programs (P40 OD010440). We thank the information resource WormBase. R.W.F. was supported by a Paul and Daisy Soros Fellowship and by NIGMS T32GM007223. K.W. was supported by the Yale STARS II program and E.Y.W. was supported by a Yale College Dean's Research Fellowship. This work was supported by NIH grants NS036918 and NS086932 to M.R.K.
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