Erratum: Betaine acts on a ligand-gated ion channel in the nervous system of the nematode C. elegans

Trimethyl glycine, or betaine, is an amino acid derivative found in diverse organisms, from bacteria to plants and animals. It can function as an osmolyte to protect cells against osmotic stress, and building evidence suggests betaine may also play important functional roles in the nervous system. However, despite growing interest in betaine's roles in the nervous system, few molecular mechanisms have been elucidated. Here we identify the expression of betaine synthesis pathway genes in the nervous system of the nematode worm, C. elegans. We show that betaine, produced in a single pair of interneurons, the RIMs, can control complex behavioural states. Moreover, we also identify and characterise a new betaine-gated inhibitory ligand gated ion channel, LGC-41, which is required for betaine related behavioural changes. Intriguingly we observed expression of LGC-41 in punctate structures across several sensory and interneurons, including those synaptically connected to the RIMs. Our data presents a neuronal molecular mechanism for the action of betaine, via a specific receptor, in the control of complex behaviour within the nervous system of C. elegans. This may suggest a much broader role for betaine in the regulation of animal nervous systems than previously recognised.

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Ultrasound elicits behavioral responses through mechanical effects on neurons and ion channels in a simple nervous system

10.1101/104463 ◽

2017 ◽

Cited By ~ 1

Author(s):

Jan Kubanek ◽

Poojan Shukla ◽

Alakananda Das ◽

Stephen A. Baccus ◽

Miriam B. Goodman

Keyword(s):

Nervous System ◽

Ion Channels ◽

Ion Channel ◽

Behavioral Responses ◽

Thermal Fluctuations ◽

Dependent Manner ◽

Wild Type ◽

Excitable Cells ◽

C Elegans ◽

Mechanical Effects

AbstractFocused ultrasound has been shown to stimulate excitable cells, but the biophysical mechanisms behind this phenomenon remain poorly understood. To provide additional insight, we devised a behavioral-genetic assay applied to the well-characterized nervous system of C. elegans nematodes. We found that pulsed ultrasound elicits robust reversal behavior in wild-type animals in a pressure-, duration-, and pulse protocol-dependent manner. Responses were preserved in mutants unable to sense thermal fluctuations and absent in mutants lacking neurons required for mechanosensation. Additionally, we found that the worm‘s response to ultrasound pulses rests on the expression of MEC-4, a DEG/ENaC/ASIC ion channel required for touch sensation. Consistent with prior studies of MEC-4-dependent currents in vivo, the worm’s response was optimal for pulses repeated 300 to 1000 times per second. Based on these findings, we conclude that mechanical, rather than thermal stimulation accounts for behavioral responses. Further, we propose that acoustic radiation force governs the response to ultrasound in a manner that depends on the touch receptor neurons and MEC-4-dependent ion channels. Our findings illuminate a complete pathway of ultrasound action, from the forces generated by propagating ultrasound to an activation of a specific ion channel. The findings further highlight the importance of optimizing ultrasound pulsing protocols when stimulating neurons via ion channels with mechanosensitive properties.Significance StatementHow ultrasound influences neurons and other excitable cells has remained a mystery for decades. Although it is widely understood that ultrasound can heat tissues and induce mechanical strain, whether or not neuronal activation depends on heat, mechanical force, or both physical factors is not known. We harnessed C. elegans nematodes and their extraordinary sensitivity to thermal and mechanical stimuli to address this question. Whereas thermosensory mutants respond to ultrasound similar to wild-type animals, mechanosensory mutants were insensitive to ultrasound stimulation. Additionally, stimulus parameters that accentuate mechanical effects were more effective than those producing more heat. These findings highlight a mechanical nature of the effect of ultrasound on neurons and suggest specific ways to optimize stimulation protocols in specific tissues.

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Acid-sensing ion channel-1 contributes to axonal degeneration in autoimmune inflammation of the central nervous system

Nature Medicine ◽

10.1038/nm1668 ◽

2007 ◽

Vol 13 (12) ◽

pp. 1483-1489 ◽

Cited By ~ 252

Author(s):

Manuel A Friese ◽

Matthew J Craner ◽

Ruth Etzensperger ◽

Sandra Vergo ◽

John A Wemmie ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Ion Channel ◽

Axonal Degeneration ◽

Autoimmune Inflammation ◽

The Central Nervous System

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Behavioral Effects of Volatile Anesthetics in Caenorhabditis elegans

Anesthesiology ◽

10.1097/00000542-199610000-00027 ◽

1996 ◽

Vol 85 (4) ◽

pp. 901-912 ◽

Cited By ~ 38

Author(s):

Michael C. Crowder ◽

Laynie D. Shebester ◽

Tim Schedl

Keyword(s):

Nervous System ◽

Caenorhabditis Elegans ◽

Time Course ◽

Model Organism ◽

Volatile Anesthetic ◽

Volatile Anesthetics ◽

Effective Concentration ◽

Forward Genetics ◽

C Elegans ◽

Median Effective Concentration

Background The nematode Caenorhabditis elegans offers many advantages as a model organism for studying volatile anesthetic actions. It has a simple, well-understood nervous system; it allows the researcher to do forward genetics; and its genome will soon be completely sequenced. C. elegans is immobilized by volatile anesthetics only at high concentrations and with an unusually slow time course. Here other behavioral dysfunctions are considered as anesthetic endpoints in C. elegans. Methods The potency of halothane for disrupting eight different behaviors was determined by logistic regression of concentration and response data. Other volatile anesthetics were also tested for some behaviors. Established protocols were used for behavioral endpoints that, except for pharyngeal pumping, were set as complete disruption of the behavior. Time courses were measured for rapid behaviors. Recovery from exposure to 1 or 4 vol% halothane was determined for mating, chemotaxis, and gross movement. All experiments were performed at 20 to 22 degrees C. Results The median effective concentration values for halothane inhibition of mating (0.30 vol%-0.21 mM), chemotaxis (0.34 vol%-0.24 mM), and coordinated movement (0.32 vol% - 0.23 mM) were similar to the human minimum alveolar concentration (MAC; 0.21 mM). In contrast, halothane produced immobility with a median effective concentration of 3.65 vol% (2.6 mM). Other behaviors had intermediate sensitivities. Halothane's effects reached steady-state in 10 min for all behaviors tested except immobility, which required 2 h. Recovery was complete after exposure to 1 vol% halothane but was significantly reduced after exposure to immobilizing concentrations. Conclusions Volatile anesthetics selectively disrupt C. elegans behavior. The potency, time course, and recovery characteristics of halothane's effects on three behaviors are similar to its anesthetic properties in vertebrates. The affected nervous system molecules may express structural motifs similar to those on vertebrate anesthetic targets.

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Complementary RNA amplification methods enhance microarray identification of transcripts expressed in the C. elegans nervous system

BMC Genomics ◽

10.1186/1471-2164-9-84 ◽

2008 ◽

Vol 9 (1) ◽

Cited By ~ 24

Author(s):

Joseph D Watson ◽

Shenglong Wang ◽

Stephen E Von Stetina ◽

W Clay Spencer ◽

Shawn Levy ◽

...

Keyword(s):

Nervous System ◽

Rna Amplification ◽

C Elegans

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Simulations of Subunit Interactions in the C. Elegans GluCl Ligand-Gated Ion Channel

Biophysical Journal ◽

10.1016/j.bpj.2011.11.2587 ◽

2012 ◽

Vol 102 (3) ◽

pp. 472a

Author(s):

Ozge Yoluk ◽

Samuel Murail ◽

Erik Lindahl

Keyword(s):

Ion Channel ◽

Subunit Interactions ◽

C Elegans

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Heparan sulfate molecules mediate synapse formation and function of male mating neural circuits in C. elegans

10.1101/277137 ◽

2018 ◽

Author(s):

María I. Lázaro-Peña ◽

Carlos A. Díaz-Balzac ◽

Hannes E. Bülow ◽

Scott W. Emmons

Keyword(s):

Nervous System ◽

Cell Adhesion ◽

Neural Cell ◽

Male Mating ◽

Synaptic Connections ◽

Adhesion Protein ◽

C Elegans ◽

Neural Cell Adhesion ◽

Heparan Sulfates ◽

And Function

AbstractThe nervous system regulates complex behaviors through a network of neurons interconnected by synapses. How specific synaptic connections are genetically determined is still unclear. Male mating is the most complex behavior in C. elegans. It is composed of sequential steps that are governed by more than 3,000 chemical connections. Here we show that heparan sulfates (HS) play a role in the formation and function of the male neural network. Cell-autonomous and non-autonomous 3-O sulfation by the HS modification enzyme HST-3.1/HS 3-O-sulfotransferase, localized to the HSPG glypicans LON-2/glypican and GPN-1/glypican, was specifically required for response to hermaphrodite contact during mating. Loss of 3-O sulfation resulted in the presynaptic accumulation of RAB-3, a molecule that localizes to synaptic vesicles, disrupting the formation of synapses in a component of the mating circuits. We also show that neural cell adhesion protein neurexin promotes and neural cell adhesion protein neuroligin inhibits formation of the same set of synapses in a parallel pathway. Thus, neural cell adhesion proteins and extracellular matrix components act together in the formation of synaptic connections.Author SummaryThe formation of the nervous system requires the function of several genetically-encoded proteins to form complex networks. Enzymatically-generated modifications of these proteins play a crucial role during this process. These authors analyzed the role of heparan sulfates in the process of synaptogenesis in the male tail of C. elegans. A modification of heparan sulfate is required for the formation of specific synapses between neurons by acting cell-autonomously and non-autonomously. Could it be that heparan sulfates and their diverse modifications are a component of the specification factor that neurons use to make such large numbers of connections unique?

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in vitro and in vivo investigation of modulators of hyperactivated ion channel induced necrosis in C. elegans

The FASEB Journal ◽

10.1096/fasebj.26.1_supplement.762.16 ◽

2012 ◽

Vol 26 (S1) ◽

Author(s):

Shaunak Kamat ◽

Laura Bianchi ◽

Shrutika Yeola ◽

Monica Driscoll

Keyword(s):

Ion Channel ◽

C Elegans

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Neuropeptides and Behaviors: How Small Peptides Regulate Nervous System Function and Behavioral Outputs

Frontiers in Molecular Neuroscience ◽

10.3389/fnmol.2021.786471 ◽

2021 ◽

Vol 14 ◽

Author(s):

Umer Saleem Bhat ◽

Navneet Shahi ◽

Siju Surendran ◽

Kavita Babu

Keyword(s):

Nervous System ◽

Behavioral Plasticity ◽

Environmental Changes ◽

Sensory Information ◽

Synaptic Activity ◽

Small Peptides ◽

C Elegans ◽

Wide Range ◽

Nervous System Function ◽

Insight Into

One of the reasons that most multicellular animals survive and thrive is because of the adaptable and plastic nature of their nervous systems. For an organism to survive, it is essential for the animal to respond and adapt to environmental changes. This is achieved by sensing external cues and translating them into behaviors through changes in synaptic activity. The nervous system plays a crucial role in constantly evaluating environmental cues and allowing for behavioral plasticity in the organism. Multiple neurotransmitters and neuropeptides have been implicated as key players for integrating sensory information to produce the desired output. Because of its simple nervous system and well-established neuronal connectome, C. elegans acts as an excellent model to understand the mechanisms underlying behavioral plasticity. Here, we critically review how neuropeptides modulate a wide range of behaviors by allowing for changes in neuronal and synaptic signaling. This review will have a specific focus on feeding, mating, sleep, addiction, learning and locomotory behaviors in C. elegans. With a view to understand evolutionary relationships, we explore the functions and associated pathophysiology of C. elegans neuropeptides that are conserved across different phyla. Further, we discuss the mechanisms of neuropeptidergic signaling and how these signals are regulated in different behaviors. Finally, we attempt to provide insight into developing potential therapeutics for neuropeptide-related disorders.

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