Reference - Detail
| RRC ID | 21797 |
|---|---|
| Author | Stawicki TM, Takayanagi-Kiya S, Zhou K, Jin Y. |
| Title | Neuropeptides function in a homeostatic manner to modulate excitation-inhibition imbalance in C. elegans. |
| Journal | PLoS Genet |
| Abstract |
Neuropeptides play crucial roles in modulating neuronal networks, including changing intrinsic properties of neurons and synaptic efficacy. We previously reported a Caenorhabditis elegans mutant, acr-2(gf), that displays spontaneous convulsions as the result of a gain-of-function mutation in a neuronal nicotinic acetylcholine receptor subunit. The ACR-2 channel is expressed in the cholinergic motor neurons, and acr-2(gf) causes cholinergic overexcitation accompanied by reduced GABAergic inhibition in the locomotor circuit. Here we show that neuropeptides play a homeostatic role that compensates for this excitation-inhibition imbalance in the locomotor circuit. Loss of function in genes required for neuropeptide processing or release of dense core vesicles specifically modulate the convulsion frequency of acr-2(gf). The proprotein convertase EGL-3 is required in the cholinergic motor neurons to restrain convulsions. Electrophysiological recordings of neuromuscular junctions show that loss of egl-3 in acr-2(gf) causes a further reduction of GABAergic inhibition. We identify two neuropeptide encoding genes, flp-1 and flp-18, that together counteract the excitation-inhibition imbalance in acr-2(gf) mutants. We further find that acr-2(gf) causes an increased expression of flp-18 in the ventral cord cholinergic motor neurons and that overexpression of flp-18 reduces the convulsion of acr-2(gf) mutants. The effects of these peptides are in part mediated by two G-protein coupled receptors, NPR-1 and NPR-5. Our data suggest that the chronic overexcitation of the cholinergic motor neurons imposed by acr-2(gf) leads to an increased production of FMRFamide neuropeptides, which act to decrease the activity level of the locomotor circuit, thereby homeostatically modulating the excitation and inhibition imbalance. |
| Volume | 9(5) |
| Pages | e1003472 |
| Published | 2013-5-1 |
| DOI | 10.1371/journal.pgen.1003472 |
| PII | PGENETICS-D-12-01995 |
| PMID | 23658528 |
| PMC | PMC3642046 |
| MeSH | Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Cholinergic Neurons / metabolism* Electrophysiological Phenomena Excitation Contraction Coupling / physiology FMRFamide / metabolism Homeostasis Male Motor Activity / physiology Motor Neurons / metabolism Motor Neurons / physiology Neuropeptides / genetics Neuropeptides / metabolism* Proprotein Convertase 2 / metabolism Receptors, Nicotinic* / genetics Receptors, Nicotinic* / metabolism Seizures / metabolism Seizures / physiopathology |
| IF | 5.175 |
| Times Cited | 29 |
| WOS Category | GENETICS & HEREDITY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 3 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | flp-11(tm2706) flp-13(tm2427) flp-18(tm2179) nlp-3(tm3023) nlp-7(tm2984) nlp-9(tm3572) nlp-14(tm1880) ins-11(tm1053) npr-4(tm1782) egl-21(tm5578) ckr-2(tm3082) |