TY - JOUR
T1 - Serotonin and neuropeptides are both released by the HSN command neuron to initiate C. elegans egg laying
AU - Brewer, Jacob C.
AU - Olson, Andrew C.
AU - Collins, Kevin M.
AU - Koelle, Michael R.
N1 - Funding Information:
This work was funded by National Institute of Neurological Disorders and Stroke (https://www.ninds.nih.gov/) grants NS036918 (to MRK) and NS086932 (to MRK and KMC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Kelly Culhane for assistance with exogenous serotonin assay, and Allison Butt for providing chromosomally-integrated nlp-3 overexrpessor transgenes. We thank Bob Horvitz (MIT) for nlp-3 (n4897), and the Japanese National BioResource Project for nlp-3 (tm3023). Additional strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440).
PY - 2019
Y1 - 2019
N2 - Neurons typically release both a small-molecule neurotransmitter and one or more neuropeptides, but how these two types of signal from the same neuron might act together remains largely obscure. For example, serotonergic neurons in mammalian brain express the neuropeptide Substance P, but it is unclear how this co-released neuropeptide might modulate serotonin signaling. We studied this issue in C. elegans, in which all serotonergic neurons express the neuropeptide NLP-3. The serotonergic Hermaphrodite Specific Neurons (HSNs) are command motor neurons within the egg-laying circuit which have been shown to release serotonin to initiate egg-laying behavior. We found that egg-laying defects in animals lacking serotonin were far milder than in animals lacking HSNs, suggesting that HSNs must release other signal(s) in addition to serotonin to stimulate egg laying. While null mutants for nlp-3 had only mild egg-laying defects, animals lacking both serotonin and NLP-3 had severe defects, similar to those of animals lacking HSNs. Optogenetic activation of HSNs induced egg laying in wild-type animals, and in mutant animals lacking either serotonin or NLP-3, but failed to induce egg laying in animals lacking both. We recorded calcium activity in the egg-laying muscles of animals lacking either serotonin, NLP-3, or both. The single mutants, and to a greater extent the double mutant, showed muscle activity that was uncoordinated and unable to expel eggs. Specifically, the vm2 muscles cells, which are direct postsynaptic targets of the HSN, failed to contract simultaneously with other egg-laying muscle cells. Our results show that the HSN neurons use serotonin and the neuropeptide NLP-3 as partially redundant co-transmitters that together stimulate and coordinate activity of the target cells onto which they are released.
AB - Neurons typically release both a small-molecule neurotransmitter and one or more neuropeptides, but how these two types of signal from the same neuron might act together remains largely obscure. For example, serotonergic neurons in mammalian brain express the neuropeptide Substance P, but it is unclear how this co-released neuropeptide might modulate serotonin signaling. We studied this issue in C. elegans, in which all serotonergic neurons express the neuropeptide NLP-3. The serotonergic Hermaphrodite Specific Neurons (HSNs) are command motor neurons within the egg-laying circuit which have been shown to release serotonin to initiate egg-laying behavior. We found that egg-laying defects in animals lacking serotonin were far milder than in animals lacking HSNs, suggesting that HSNs must release other signal(s) in addition to serotonin to stimulate egg laying. While null mutants for nlp-3 had only mild egg-laying defects, animals lacking both serotonin and NLP-3 had severe defects, similar to those of animals lacking HSNs. Optogenetic activation of HSNs induced egg laying in wild-type animals, and in mutant animals lacking either serotonin or NLP-3, but failed to induce egg laying in animals lacking both. We recorded calcium activity in the egg-laying muscles of animals lacking either serotonin, NLP-3, or both. The single mutants, and to a greater extent the double mutant, showed muscle activity that was uncoordinated and unable to expel eggs. Specifically, the vm2 muscles cells, which are direct postsynaptic targets of the HSN, failed to contract simultaneously with other egg-laying muscle cells. Our results show that the HSN neurons use serotonin and the neuropeptide NLP-3 as partially redundant co-transmitters that together stimulate and coordinate activity of the target cells onto which they are released.
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U2 - 10.1371/journal.pgen.1007896
DO - 10.1371/journal.pgen.1007896
M3 - Article
C2 - 30677018
AN - SCOPUS:85061112200
VL - 15
JO - PLoS Genetics
JF - PLoS Genetics
SN - 1553-7390
IS - 1
M1 - e1007896
ER -