scholarly journals Knockout of glial channel ACD-1 exacerbates sensory deficits in a C. elegans mutant by regulating calcium levels of sensory neurons

2012 ◽  
Vol 107 (1) ◽  
pp. 148-158 ◽  
Author(s):  
Ying Wang ◽  
Giulia D'Urso ◽  
Laura Bianchi
Keyword(s):  
Sensory Neurons ◽  
Neuronal Excitability ◽  
Sensory Deficits ◽  
C Elegans ◽  
Hypomorphic Allele ◽  
Low Concentrations ◽  
Wide Range ◽  
Gated Channel ◽  
Intracellular Ca

Degenerin/epithelial Na+ channels (DEG/ENaCs) are voltage-independent Na+ or Na+/Ca2+ channels expressed in many tissues and are needed for a wide range of physiological functions, including sensory perception and transepithelial Na+ transport. In the nervous system, DEG/ENaCs are expressed in both neurons and glia. However, the role of glial vs. neuronal DEG/ENaCs remains unclear. We recently reported the characterization of a novel DEG/ENaC in Caenorhabditis elegans that we named ACD-1. ACD-1 is expressed in glial amphid sheath cells. The glial ACD-1, together with the neuronal DEG/ENaC DEG-1, is necessary for acid avoidance and attraction to lysine. We report presently that knockout of acd-1 in glia exacerbates sensory deficits caused by another mutant: the hypomorphic allele of the cGMP-gated channel subunit tax-2. Furthermore, sensory deficits caused by mutations in Gi protein odr-3 and guanylate cyclase daf-11, which regulate the activity of TAX-2/TAX-4 channels, are worsened by knockout of acd-1. We also show that sensory neurons of acd-1 tax-2(p694) double mutants fail to undergo changes in intracellular Ca2+ when animals are exposed to low concentrations of attractant. Finally, we show that exogenous expression of TRPV1 in sensory neurons and exposure to capsaicin rescue sensory deficits of acd-1 tax-2(p694) mutants, suggesting that sensory deficits of these mutants are bypassed by increasing neuronal excitability. Our data suggest a role of glial DEG/ENaC channel ACD-1 in supporting neuronal activity.

scholarly journals Bacterial second messenger 3′,5′-cyclic diguanylate attracts Caenorhabditis elegans and suppresses its immunity

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Joseph Angeloni ◽  
Yuqing Dong ◽  
Zeneng Wang ◽  
Min Cao
Keyword(s):  
Caenorhabditis Elegans ◽  
High Rate ◽  
Bacterial Invasion ◽  
Signal Molecules ◽  
Cyclic Diguanylate ◽  
C Elegans ◽  
Low Concentrations ◽  
Wide Range ◽  
Interkingdom Communication

AbstractCyclic di-nucleotides are important secondary signaling molecules in bacteria that regulate a wide range of processes. In this study, we found that Caenorhabditis elegans can detect and are attracted to multiple signal molecules produced by Vibrio cholerae, specifically the 3′,5′-cyclic diguanylate (c-di-GMP), even though this bacterium kills the host at a high rate. C-di-GMP is sensed through C. elegans olfactory AWC neurons, which then evokes a series of signal transduction pathways that lead to reduced activity of two key stress response transcription factors, SKN-1 and HSF-1, and weakened innate immunity. Taken together, our study elucidates the role of c-di-GMP in interkingdom communication. For C. elegans, bacterial c-di-GMP may serve as a cue that they can use to detect food. On the other hand, preexposure to low concentrations of c-di-GMP may impair their immune response, which could facilitate bacterial invasion and survival.

scholarly journals The DBL-1/TGF-β signaling pathway regulates pathogen-specific innate immune responses in C. elegans

2021 ◽  
Author(s):  
Bhoomi Madhu ◽  
Tina L. Gumienny
Keyword(s):  
Innate Immunity ◽  
Immune Responses ◽  
Signaling Pathway ◽  
Defense Responses ◽  
C Elegans ◽  
Host Immune Responses ◽  
Wide Range ◽  
Independent Functions ◽  
Multiple Cell

Innate immunity in animals is orchestrated by multiple cell signaling pathways, including the TGF-β; superfamily pathway. While the role of TGF-β signaling in innate immunity has been clearly identified, the requirement for this pathway in generating specific, robust responses to different bacterial challenges has not been characterized. Here, we address the role of DBL-1/TGF-β in regulating signature host defense responses to a wide range of bacteria in C. elegans. This work reveals a role of DBL-1/TGF-β in animal survival, organismal behaviors, and molecular responses in different environments. Additionally, we identify a novel role for SMA-4/Smad that suggests both DBL-1/TGF-β-dependent and -independent functions in host avoidance responses. RNA-seq analyses and immunity reporter studies indicate DBL-1/TGF-β differentially regulates target gene expression upon exposure to different bacteria. Furthermore, the DBL-1/TGF-β pathway is itself differentially affected by the bacteria exposure. Collectively, these findings demonstrate bacteria-specific host immune responses regulated by the DBL-1/TGF-β signaling pathway.

scholarly journals C. elegans-based chemosensation strategy for the early detection of cancer metabolites in urine samples

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Enrico Lanza ◽  
Martina Di Rocco ◽  
Silvia Schwartz ◽  
Davide Caprini ◽  
Edoardo Milanetti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Sensory Neurons ◽  
Calcium Imaging ◽  
Sensory Modality ◽  
High Accuracy ◽  
Urine Samples ◽  
C Elegans ◽  
Chemosensory Receptors ◽  
Wide Range ◽  
Behavioral Assays

AbstractChemosensory receptors play a crucial role in distinguishing the wide range of volatile/soluble molecules by binding them with high accuracy. Chemosensation is the main sensory modality in organisms lacking long-range sensory mechanisms like vision/hearing. Despite its low number of sensory neurons, the nematode Caenorhabditis elegans possesses several chemosensory receptors, allowing it to detect about as many odorants as mammals. Here, we show that C. elegans displays attraction towards urine samples of women with breast cancer, avoiding control ones. Behavioral assays on animals lacking AWC sensory neurons demonstrate the relevance of these neurons in sensing cancer odorants: calcium imaging on AWC increases the accuracy of the discrimination (97.22%). Also, chemotaxis assays on animals lacking GPCRs expressed in AWC allow to identify receptors involved in binding cancer metabolites, suggesting that an alteration of a few metabolites is sufficient for the cancer discriminating behavior of C. elegans, which may help identify a fundamental fingerprint of breast cancer.

scholarly journals Historical Perspective: Models of Parkinson’s Disease

2020 ◽  
Vol 21 (7) ◽  
pp. 2464 ◽  
Author(s):  
Shyh Jenn Chia ◽  
Eng-King Tan ◽  
Yin-Xia Chao
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Genetic Manipulation ◽  
Disease Model ◽  
Transgenic Models ◽  
C Elegans ◽  
Wide Range ◽  
Therapeutic Development ◽  
6 Hydroxydopamine

Parkinson’s disease (PD) is the most common movement disorder with motor and nonmotor signs. The current therapeutic regimen for PD is mainly symptomatic as the etio-pathophysiology has not been fully elucidated. A variety of animal models has been generated to study different aspects of the disease for understanding the pathogenesis and therapeutic development. The disease model can be generated through neurotoxin-based or genetic-based approaches in a wide range of animals such as non-human primates (NHP), rodents, zebrafish, Caenorhabditis (C.) elegans, and drosophila. Cellular-based disease model is frequently used because of the ease of manipulation and suitability for large-screen assays. In neurotoxin-induced models, chemicals such as 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), rotenone, and paraquat are used to recapitulate the disease. Genetic manipulation of PD-related genes, such as α-Synuclein(SNCA), Leucine-rich repeat kinase 2 (LRRK2), Pten-Induced Kinase 1 (PINK1), Parkin(PRKN), and Protein deglycase (DJ-1) Are used in the transgenic models. An emerging model that combines both genetic- and neurotoxin-based methods has been generated to study the role of the immune system in the pathogenesis of PD. Here, we discuss the advantages and limitations of the different PD models and their utility for different research purposes.

scholarly journals Twitchy, the Drosophila orthologue of the ciliary gating protein FBF1/dyf-19, is required for coordinated locomotion and male fertility

Biology Open ◽  
2021 ◽  
Author(s):  
Suzanne H Hodge ◽  
Amy Watts ◽  
Richard Marley ◽  
Richard A Baines ◽  
Ernst Hafen ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Primary Cilia ◽  
Loss Of Function ◽  
Transmembrane Receptors ◽  
C Elegans ◽  
Male Germline ◽  
Sensory Cilia ◽  
Import And Export ◽  
Flagellar Axoneme

Primary cilia are compartmentalised from the rest of the cell by a ciliary gate comprising transition fibres and a transition zone. The ciliary gate allows the selective import and export of molecules such as transmembrane receptors and transport proteins. These are required for the assembly of the cilium, its function as a sensory and signalling centre and to maintain its distinctive composition. Certain motile cilia can also form within the cytosol as exemplified by human and Drosophila sperm. The role of transition fibre proteins has not been well described in the cytoplasmic cilia. Drosophila have both compartmentalized primary cilia, in sensory neurons, and sperm flagella that form within the cytosol. Here, we describe phenotypes for twitchy the Drosophila orthologue of a transition fibre protein, mammalian FBF1/C. elegans dyf-19. Loss-of-function mutants in twitchy are adult lethal and display a severely uncoordinated phenotype. Twitchy flies are too uncoordinated to mate but RNAi-mediated loss of twitchy specifically within the male germline results in coordinated but infertile adults. Examination of sperm from twitchy RNAi-knockdown flies shows that the flagellar axoneme forms, elongates and is post-translationally modified by polyglycylation but the production of motile sperm is impaired. These results indicate that twitchy is required for the function of both sensory cilia that are compartmentalized from the rest of the cell and sperm flagella that are formed within the cytosol of the cell. Twitchy is therefore likely to function as part of a molecular gate in sensory neurons but may have a distinct function in sperm cells.

scholarly journals Revisiting PNS Plasticity: How Uninjured Sensory Afferents Promote Neuropathic Pain

2020 ◽  
Vol 14 ◽  
Author(s):  
Emily L. Tran ◽  
LaTasha K. Crawford
Keyword(s):  
Neuropathic Pain ◽  
Nerve Injury ◽  
Sensory Neurons ◽  
Sensory Ganglia ◽  
Intercellular Signaling ◽  
Sensory Afferents ◽  
Pain Mechanisms ◽  
Wide Range ◽  
Cell Type Specific

Despite the widespread study of how injured nerves contribute to chronic pain, there are still major gaps in our understanding of pain mechanisms. This is particularly true of pain resulting from nerve injury, or neuropathic pain, wherein tactile or thermal stimuli cause painful responses that are particularly difficult to treat with existing therapies. Curiously, this stimulus-driven pain relies upon intact, uninjured sensory neurons that transmit the signals that are ultimately sensed as painful. Studies that interrogate uninjured neurons in search of cell-specific mechanisms have shown that nerve injury alters intact, uninjured neurons resulting in an activity that drives stimulus-evoked pain. This review of neuropathic pain mechanisms summarizes cell-type-specific pathology of uninjured sensory neurons and the sensory ganglia that house their cell bodies. Uninjured neurons have demonstrated a wide range of molecular and neurophysiologic changes, many of which are distinct from those detected in injured neurons. These intriguing findings include expression of pain-associated molecules, neurophysiological changes that underlie increased excitability, and evidence that intercellular signaling within sensory ganglia alters uninjured neurons. In addition to well-supported findings, this review also discusses potential mechanisms that remain poorly understood in the context of nerve injury. This review highlights key questions that will advance our understanding of the plasticity of sensory neuron subpopulations and clarify the role of uninjured neurons in developing anti-pain therapies.

Phenotypic characterization of gastric sensory neurons in mice

2006 ◽  
Vol 291 (5) ◽  
pp. G987-G997 ◽  
Author(s):  
Klaus Bielefeldt ◽  
Fang Zhong ◽  
H. Richard Koerber ◽  
Brian M. Davis
Keyword(s):  
Sensory Neurons ◽  
Transient Receptor Potential ◽  
Vagal Afferents ◽  
Phenotypic Characterization ◽  
Transient Receptor Potential Vanilloid ◽  
Mechanical Stimuli ◽  
Wide Range ◽  
Stimulation Of

Recent studies suggest that the capsaicin receptor [transient receptor potential vanilloid (TRPV)1] may play a role in visceral mechanosensation. To address the potential role of TRPV1 in vagal sensory neurons, we developed a new in vitro technique allowing us to determine TRPV1 expression directly in physiologically characterized gastric sensory neurons. Stomach, esophagus, and intact vagus nerve up to the central terminations were carefully dissected and placed in a perfusion chamber. Intracellular recordings were made from the soma of nodose neurons during mechanical stimulation of the stomach. Physiologically characterized neurons were labeled iontophoretically with neurobiotin and processed for immunohistochemical experiments. As shown by action potential responses triggered by stimulation of the upper thoracic vagus with a suction electrode, essentially all abdominal vagal afferents in mice conduct in the C-fiber range. Mechanosensitive gastric afferents encode stimulus intensities over a wide range without apparent saturation when punctate stimuli are used. Nine of 37 mechanosensitive vagal afferents expressed TRPV1 immunoreactivity, with 8 of the TRPV1-positive cells responding to stretch. A small number of mechanosensitive gastric vagal afferents express neurofilament heavy chains and did not respond to stretch. By maintaining the structural and functional integrity of vagal afferents up to the nodose ganglion, physiological and immunohistochemical properties of mechanosensory gastric sensory neurons can be studied in vitro. Using this novel technique, we identified TRPV1 immunoreactivity in only one-fourth of gastric mechanosensitive neurons, arguing against a major role of this ion channel in sensation of mechanical stimuli under physiological conditions.

scholarly journals C. elegans-based chemosensation strategy for the early detection of cancer metabolites in urine samples

2021 ◽  
Author(s):  
Enrico Lanza ◽  
Martina Di Rocco ◽  
Silvia Schwartz ◽  
Davide Caprini ◽  
Edoardo Milanetti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Sensory Neurons ◽  
Calcium Imaging ◽  
High Accuracy ◽  
Urine Samples ◽  
Nematode Caenorhabditis Elegans ◽  
C Elegans ◽  
Chemosensory Receptors ◽  
Wide Range ◽  
Behavioral Assays

Abstract Chemosensory receptors play a crucial role in distinguishing the wide range of volatile/soluble molecules by binding them with high accuracy. Chemosensation is particularly developed in organisms lacking long-range sensory mechanisms like vision/hearing. Despite its low number of sensory neurons, the nematode Caenorhabditis elegans possesses several chemosensory receptors, allowing it to detect about as many odorants as mammals. Here, we show that C. elegans displays attraction towards urine samples of women with breast cancer, avoiding control ones. Behavioral assays on animals lacking AWC sensory neurons demonstrate the relevance of these neurons in sensing cancer odorants: calcium imaging on AWC increases the accuracy of the discrimination (97.22%). Also, chemotaxis assays on animals lacking GPCRs expressed in AWC allow to identify receptors involved in binding cancer metabolites, suggesting that an alteration of a few metabolites is sufficient for the cancer discriminating behavior of C. elegans, which may help identify a fundamental fingerprint of breast cancer.

scholarly journals Plasticity in gustatory and nociceptive neurons controls decision making in C. elegans salt navigation

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Martijn P. J. Dekkers ◽  
Felix Salfelder ◽  
Tom Sanders ◽  
Oluwatoroti Umuerri ◽  
Netta Cohen ◽  
...  
Keyword(s):  
Decision Making ◽  
Cognitive Processing ◽  
Sensory Neurons ◽  
Sensory Adaptation ◽  
Nociceptive Neurons ◽  
C Elegans ◽  
Motor Behaviors ◽  
Adaptation Mechanisms ◽  
Multiple Cell

AbstractA conventional understanding of perception assigns sensory organs the role of capturing the environment. Better sensors result in more accurate encoding of stimuli, allowing for cognitive processing downstream. Here we show that plasticity in sensory neurons mediates a behavioral switch in C. elegans between attraction to NaCl in naïve animals and avoidance of NaCl in preconditioned animals, called gustatory plasticity. Ca2+ imaging in ASE and ASH NaCl sensing neurons reveals multiple cell-autonomous and distributed circuit adaptation mechanisms. A computational model quantitatively accounts for observed behaviors and reveals roles for sensory neurons in the control and modulation of motor behaviors, decision making and navigational strategy. Sensory adaptation dynamically alters the encoding of the environment. Rather than encoding the stimulus directly, therefore, we propose that these C. elegans sensors dynamically encode a context-dependent value of the stimulus. Our results demonstrate how adaptive sensory computation can directly control an animal’s behavioral state.

scholarly journals Plasticity in gustatory and nociceptive neurons controls decision making in C. elegans salt navigation

2021 ◽  
Author(s):  
Martijn P.J. Dekkers ◽  
Felix Salfelder ◽  
Tom Sanders ◽  
Oluwatoroti Umuerri ◽  
Netta Cohen ◽  
...  
Keyword(s):  
Decision Making ◽  
Cognitive Processing ◽  
Sensory Neurons ◽  
Sensory Adaptation ◽  
Nociceptive Neurons ◽  
C Elegans ◽  
Motor Behaviors ◽  
Adaptation Mechanisms ◽  
Multiple Cell

A conventional understanding of perception assigns sensory organs the role of capturing the environment. Better sensors result in more accurate encoding of stimuli, allowing for cognitive processing downstream. Here we show that plasticity in sensory neurons mediates a behavioral switch in C. elegans between attraction to NaCl in naive animals and avoidance of NaCl in preconditioned animals, called gustatory plasticity. Ca2+ imaging in ASE and ASH NaCl sensing neurons reveals multiple cell-autonomous and distributed circuit adaptation mechanisms. A computational model quantitatively accounts for observed behaviors and reveals roles for sensory neurons in the control and modulation of motor behaviors, decision making and navigational strategy. Sensory adaptation dynamically alters the encoding of the environment. Rather than encoding the stimulus directly, therefore, we propose that these C. elegans sensors dynamically encode a context-dependent value of the stimulus. Our results demonstrate how adaptive sensory computation can directly control an animal′s behavioral state.

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