論文 - 詳細
| RRC ID | 59517 |
|---|---|
| 著者 | Katz M, Corson F, Keil W, Singhal A, Bae A, Lu Y, Liang Y, Shaham S. |
| タイトル | Glutamate spillover in C. elegans triggers repetitive behavior through presynaptic activation of MGL-2/mGluR5. |
| ジャーナル | Nat Commun |
| Abstract |
Glutamate is a major excitatory neurotransmitter, and impaired glutamate clearance following synaptic release promotes spillover, inducing extra-synaptic signaling. The effects of glutamate spillover on animal behavior and its neural correlates are poorly understood. We developed a glutamate spillover model in Caenorhabditis elegans by inactivating the conserved glial glutamate transporter GLT-1. GLT-1 loss drives aberrant repetitive locomotory reversal behavior through uncontrolled oscillatory release of glutamate onto AVA, a major interneuron governing reversals. Repetitive glutamate release and reversal behavior require the glutamate receptor MGL-2/mGluR5, expressed in RIM and other interneurons presynaptic to AVA. mgl-2 loss blocks oscillations and repetitive behavior; while RIM activation is sufficient to induce repetitive reversals in glt-1 mutants. Repetitive AVA firing and reversals require EGL-30/Gαq, an mGluR5 effector. Our studies reveal that cyclic autocrine presynaptic activation drives repetitive reversals following glutamate spillover. That mammalian GLT1 and mGluR5 are implicated in pathological motor repetition suggests a common mechanism controlling repetitive behaviors. |
| 巻・号 | 10(1) |
| ページ | 1882 |
| 公開日 | 2019-4-23 |
| DOI | 10.1038/s41467-019-09581-4 |
| PII | 10.1038/s41467-019-09581-4 |
| PMID | 31015396 |
| PMC | PMC6478929 |
| MeSH | Animals Animals, Genetically Modified Behavior, Animal / physiology* Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / metabolism* Datasets as Topic Excitatory Amino Acid Transporter 2 / metabolism Gene Expression Profiling Glutamic Acid / metabolism* Interneurons / metabolism Locomotion / physiology Models, Animal Presynaptic Terminals / physiology* Receptor, Metabotropic Glutamate 5 Receptors, Metabotropic Glutamate / genetics Receptors, Metabotropic Glutamate / metabolism* |
| IF | 11.878 |
| 引用数 | 5 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 16 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm355 tm1811 |