ArticleGenetics2015
An evolutionarily conserved switch in response to GABA affects development and behavior of the locomotor circuit of Caenorhabditis elegans.
Article in Genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 41 citations in OpenAlex.
- Article
- Selective optogenetic inhibition of GαProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Bidirectional Regulation of GABALife (Basel, Switzerland) · 2024Review
- The Role of Oxytocin in Abnormal Brain Development: Effect on Glial Cells and Neuroinflammation.Cells · 2022Review
- Transcriptomic analyses implicate neuronal plasticity and chloride homeostasis in ivermectin resistance and response to treatment in a parasitic nematode.PLoS pathogens · 2022Article
- Caenorhabditis elegans provides an efficient drug screening platform for GNAO1-related disorders and highlights the potential role of caffeine in controlling dyskinesia.Human molecular genetics · 2022Article
- The transforming growth factor beta ligand TIG-2 modulates the function of neuromuscular junction and muscle energy metabolism inFrontiers in molecular neuroscience · 2022Article
- Article
- A limited role of NKCC1 in telencephalic glutamatergic neurons for developing hippocampal network dynamics and behavior.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Metolazone upregulates mitochondrial chaperones and extends lifespan in Caenorhabditis elegans.Biogerontology · 2021Article
- Combining single-cell RNA-sequencing with a molecular atlas unveils new markers for Caenorhabditis elegans neuron classes.Nucleic acids research · 2020Article
- LIN-12/Notch Regulates GABA Signaling at theG3 (Bethesda, Md.) · 2018Article
- Transcranial Magnetic Stimulation in Tourette Syndrome: A Historical Perspective, Its Current Use and the Influence of Comorbidities in Treatment Response.Brain sciences · 2018Review
- Building stereotypic connectivity: mechanistic insights into structural plasticity from C. elegans.Current opinion in neurobiology · 2018Review
- Excitatory neurons sculpt GABAergic neuronal connectivity in theDevelopment (Cambridge, England) · 2017Article
- Inactivation of GABAA receptor is related to heat shock stress response in organism model Caenorhabditis elegans.Cell stress & chaperones · 2016Article
- An Optogenetic Approach for Investigation of Excitatory and Inhibitory Network GABA Actions in Mice Expressing Channelrhodopsin-2 in GABAergic Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- A Change in the Ion Selectivity of Ligand-Gated Ion Channels Provides a Mechanism to Switch Behavior.PLoS biology · 2015Article
- Synaptic remodeling, lessons fromJournal of neurogeneticsArticle
- Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.