A cellular and regulatory map of the GABAergic nervous system of C. elegans

Gendrel, Marie; Atlas, Emily G; Hobert, Oliver

doi:10.7554/elife.17686

Cited by 152 publications

(160 citation statements)

References 97 publications

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“…Despite a deep understanding of anatomy [27][28][29][30][31] and theoretical studies [32][33][34], direct experimental evidence that addresses the potential existence and identity of C. elegans CPGs has been lacking. Obtaining a mechanistic understanding of the C. elegans motor rhythm has been difficult.…”

Section: Cpgs For Body Bending Reside In the C Elegans Ventral Nervementioning

confidence: 99%

Caenorhabditis elegans excitatory ventral cord motor neurons derive rhythm for body undulation

Wen

Gao

Zhen

2018

Phil. Trans. R. Soc. B

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The intrinsic oscillatory activity of central pattern generators underlies motor rhythm. We review and discuss recent findings that address the origin of motor rhythm. These studies propose that the A- and mid-body B-class excitatory motor neurons at the ventral cord function as non-bursting intrinsic oscillators to underlie body undulation during reversal and forward movements, respectively. Proprioception entrains their intrinsic activities, allows phase-coupling between members of the same class motor neurons, and thereby facilitates directional propagation of undulations. Distinct pools of premotor interneurons project along the ventral nerve cord to innervate all members of the A- and B-class motor neurons, modulating their oscillations, as well as promoting their bi-directional coupling. The two motor sub-circuits, which consist of oscillators and descending inputs with distinct properties, form the structural base of dynamic rhythmicity and flexible partition of the forward and backward motor states. These results contribute to a continuous effort to establish a mechanistic and dynamic model of the sensorimotor system. exhibits rich sensorimotor functions despite a small neuron number. These findings implicate a circuit-level functional compression. By integrating the role of rhythm generation and proprioception into motor neurons, and the role of descending regulation of oscillators into premotor interneurons, this numerically simple nervous system can achieve a circuit infrastructure analogous to that of anatomically complex systems. has manifested itself as a compact model to search for general principles of sensorimotor behaviours.This article is part of a discussion meeting issue 'Connectome to behaviour: modelling at cellular resolution'.

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Section: Cpgs For Body Bending Reside In the C Elegans Ventral Nervementioning

confidence: 99%

Caenorhabditis elegans excitatory ventral cord motor neurons derive rhythm for body undulation

Wen

Gao

Zhen

2018

Phil. Trans. R. Soc. B

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“…However, it is not clear whether GABA and other microbiota-produced neuroactive molecules may exert their effect by localized or systemic activation of signaling pathways. In C. elegans, the number and type of GABA-containing cells and cells expressing GABA-uptake proteins and receptors are higher than previously thought and include nonneuronal cells [44]. Thus, although no intestinal GABAergic cells were reported, GABA could be pleiotropically sensed by a number of cells.…”

Section: Bacterial Gaba Is Neuroprotectivementioning

confidence: 89%

Bacterially produced metabolites protect C. elegans neurons from degeneration

et al. 2020

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Caenorhabditis elegans and its cognate bacterial diet comprise a reliable, widespread model to study diet and microbiota effects on host physiology. Nonetheless, how diet influences the rate at which neurons die remains largely unknown. A number of models have been used in C. elegans as surrogates for neurodegeneration. One of these is a C. elegans strain expressing a neurotoxic allele of the mechanosensory abnormality protein 4 (MEC-4d) degenerin/epithelial Na + (DEG/ENaC) channel, which causes the progressive degeneration of the touch receptor neurons (TRNs). Using this model, our study evaluated the effect of various dietary bacteria on neurodegeneration dynamics. Although degeneration of TRNs was steady and completed at adulthood in the strain routinely used for C. elegans maintenance (Escherichia coli OP50), it was significantly reduced in environmental and other laboratory bacterial strains. Strikingly, neuroprotection reached more than 40% in the E. coli HT115 strain. HT115 protection was long lasting well into old age of animals and was not restricted to the TRNs. Small amounts of HT115 on OP50 bacteria as well as UV-killed HT115 were still sufficient to produce neuroprotection. Early growth of worms in HT115 protected neurons from degeneration during later growth in OP50. HT115 diet promoted the nuclear translocation of DAF-16 (ortholog of the FOXO family of transcription factors), a phenomenon previously reported to underlie neuroprotection caused by downregulation of the insulin receptor in this system. Moreover, a daf-16 loss-of-function mutation abolishes HT115-driven neuroprotection. Comparative genomics, transcriptomics, and metabolomics approaches pinpointed the neurotransmitter γ-aminobutyric acid (GABA) and lactate as metabolites differentially produced between E. coli HT115 and OP50. HT115 mutant lacking glutamate decarboxylase enzyme genes (gad), which catalyze the conversion of GABA from glutamate, lost the ability to produce GABA and also to stop neurodegeneration. Moreover, in situ GABA supplementation or heterologous expression of glutamate decarboxylase in E. coli OP50 conferred neuroprotective activity to this strain. Specific C. elegans GABA transporters and receptors were required for full PLOS BIOLOGY PLOS Biology | https://doi.

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“…Neural circuits have also been identified that mediate detection and response to additional sensory stimuli including UV light, O 2 and CO 2 concentrations, electric fields, and more (Bretscher et al, 2011;Chang, Chronis, Karow, Marletta, & Bargmann, 2006;Gabel et al, 2007;Ward, Liu, Feng, & Xu, 2008). To supplement the connectome to add greater functionality, C. elegans researchers have gradually uncovered the identity of neurons that release specific neurotransmitters or express particular receptors; for example, neurons throughout the C. elegans nervous system have been identified for acetylcholine and GABA transmitter signaling (Gendrel, Atlas, & Hobert, 2016;Pereira et al, 2015; see http://www.openworm.org resource to visualize). Clear definitions of behavioral output, combined with anatomical wiring and synaptic communication, has allowed for proposed models of overall nervous system organization; for instance, coincident detection and/or a hub-and-spoke model (Ghosh, Nitabach, Zhang, & Harris, 2017).…”

Section: Neural Circuits and Behaviormentioning

confidence: 99%

Working with Worms: Caenorhabditis elegans as a Model Organism

Meneely

Dahlberg

Rose

2019

CP Essential Lab Tech

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Since its introduction as a laboratory organism 50 years ago, the nematode worm Caenorhabditis elegans has become one of the most widely used and versatile models for nearly all aspects of biological and genomic research. Many experiments in C. elegans begin with the generation and analysis of mutants that affect a specific biological process, so genetic techniques are the foundation of worm research. Many different aspects of biology are being studied in C. elegans, and three different recent Nobel Prizes have recognized six researchers working with worms. In addition, C. elegans was the first multicellular organism to have its genome sequenced, so many of the standard genomic methods have also been pioneered in C. elegans. In fact, many novel techniques and ideas are initially tested in C. elegans because of its versatility as a research organism. It is also appropriate for introducing undergraduate students to research, and some of its strengths and challenges for this purpose are discussed. © 2019 The Authors.

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A cellular and regulatory map of the GABAergic nervous system of C. elegans

Cited by 152 publications

References 97 publications

Caenorhabditis elegans excitatory ventral cord motor neurons derive rhythm for body undulation

Caenorhabditis elegans excitatory ventral cord motor neurons derive rhythm for body undulation

Bacterially produced metabolites protect C. elegans neurons from degeneration

Working with Worms: Caenorhabditis elegans as a Model Organism

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