論文 - 詳細
| RRC ID | 45572 |
|---|---|
| 著者 | Han B, Bellemer A, Koelle MR. |
| タイトル | An evolutionarily conserved switch in response to GABA affects development and behavior of the locomotor circuit of Caenorhabditis elegans. |
| ジャーナル | Genetics |
| Abstract |
The neurotransmitter gamma-aminobutyric acid (GABA) is depolarizing in the developing vertebrate brain, but in older animals switches to hyperpolarizing and becomes the major inhibitory neurotransmitter in adults. We discovered a similar developmental switch in GABA response in Caenorhabditis elegans and have genetically analyzed its mechanism and function in a well-defined circuit. Worm GABA neurons innervate body wall muscles to control locomotion. Activation of GABAA receptors with their agonist muscimol in newly hatched first larval (L1) stage animals excites muscle contraction and thus is depolarizing. At the mid-L1 stage, as the GABAergic neurons rewire onto their mature muscle targets, muscimol shifts to relaxing muscles and thus has switched to hyperpolarizing. This muscimol response switch depends on chloride transporters in the muscles analogous to those that control GABA response in mammalian neurons: the chloride accumulator sodium-potassium-chloride-cotransporter-1 (NKCC-1) is required for the early depolarizing muscimol response, while the two chloride extruders potassium-chloride-cotransporter-2 (KCC-2) and anion-bicarbonate-transporter-1 (ABTS-1) are required for the later hyperpolarizing response. Using mutations that disrupt GABA signaling, we found that neural circuit development still proceeds to completion but with an ∼6-hr delay. Using optogenetic activation of GABAergic neurons, we found that endogenous GABAA signaling in early L1 animals, although presumably depolarizing, does not cause an excitatory response. Thus a developmental depolarizing-to-hyperpolarizing shift is an ancient conserved feature of GABA signaling, but existing theories for why this shift occurs appear inadequate to explain its function upon rigorous genetic analysis of a well-defined neural circuit. |
| 巻・号 | 199(4) |
| ページ | 1159-72 |
| 公開日 | 2015-4-1 |
| DOI | 10.1534/genetics.114.173963 |
| PII | genetics.114.173963 |
| PMID | 25644702 |
| PMC | PMC4391577 |
| MeSH | Animals Anion Transport Proteins / genetics Anion Transport Proteins / metabolism Caenorhabditis elegans / growth & development Caenorhabditis elegans / metabolism* Caenorhabditis elegans / physiology Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism GABA-A Receptor Agonists / pharmacology GABAergic Neurons / drug effects GABAergic Neurons / metabolism* GABAergic Neurons / physiology K Cl- Cotransporters Locomotion* Membrane Potentials Muscimol / pharmacology Mutation Receptors, GABA-A / metabolism* Solute Carrier Family 12, Member 2 / genetics Solute Carrier Family 12, Member 2 / metabolism Symporters / genetics Symporters / metabolism Synaptic Transmission gamma-Aminobutyric Acid / metabolism* |
| IF | 4.015 |
| 引用数 | 8 |
| WOS 分野 | GENETICS & HEREDITY |
| 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 | X(Twitter) |
| 各媒体での言及数の合計 | 4 |
| 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 | tm1406 tm1165 |