scholarly journals Multiple sensory neurons mediate starvation-dependent aversive navigation inCaenorhabditis elegans

2019 ◽  
Vol 116 (37) ◽  
pp. 18673-18683 ◽  
Author(s):  
Moon Sun Jang ◽  
Yu Toyoshima ◽  
Masahiro Tomioka ◽  
Hirofumi Kunitomo ◽  
Yuichi Iino
Keyword(s):  
Sensory Neurons ◽  
Salt Concentration ◽  
Sensory Input ◽  
Sensory Information ◽  
Neural Mechanisms ◽  
Soil Nematode ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Migration Direction ◽  
Freely Moving

Animals demonstrate flexible behaviors through associative learning based on their experiences. Deciphering the neural mechanisms for sensing and integrating multiple types of sensory information is critical for understanding such behavioral controls. The soil nematodeCaenorhabditis elegansavoids salt concentrations it has previously experienced under starvation conditions. Here, we identify a pair of sensory neurons, the ASG neuron pair, which in cooperation with the ASER salt-sensing neuron generate starvation-dependent salt avoidance. Animals whose sensory input is restricted to only ASER failed to show learned avoidance due to inappropriately directed navigation behaviors. However, their navigation through a salt concentration gradient was improved by allowing sensory inputs to ASG in addition to ASER. Detailed behavioral analyses of these animals revealed that input from ASG neurons is required not only for controlling the frequency of initiating a set of sharp turns (called pirouettes) based on detected ambient salt concentrations but also adjusting the migration direction during pirouettes. Optogenetic activation of ASER by ChR2 induced turning behaviors in a salt concentration-dependent manner where presence of intact ASG was important for the starvation-dependent responses. Calcium imaging of the activity of ASG neurons in freely moving worms revealed that ASG is activated upon turning behavior. Our results indicate that ASG neurons cooperate with the ASER neuron to generate destination-directed reorientation in starvation-associated salt concentration avoidance.

scholarly journals Sphingosine 1-phosphate receptor 2 antagonist JTE-013 increases the excitability of sensory neurons independently of the receptor

2012 ◽  
Vol 108 (5) ◽  
pp. 1473-1483 ◽  
Author(s):  
Chao Li ◽  
Xian Xuan Chi ◽  
Wenrui Xie ◽  
J. A. Strong ◽  
J.-M. Zhang ◽  
...  
Keyword(s):  
G Protein ◽  
Sensory Neurons ◽  
Neuronal Excitability ◽  
Small Diameter ◽  
G Protein Coupled Receptors ◽  
Prostaglandin E ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Sphingosine 1 Phosphate ◽  
G Protein Coupled

Previously we demonstrated that sphingosine 1-phosphate receptor 1 (S1PR1) played a prominent, but not exclusive, role in enhancing the excitability of small-diameter sensory neurons, suggesting that other S1PRs can modulate neuronal excitability. To examine the potential role of S1PR2 in regulating neuronal excitability we used the established selective antagonist of S1PR2, JTE-013. Here we report that exposure to JTE-013 alone produced a significant increase in excitability in a time- and concentration-dependent manner in 70–80% of recorded neurons. Internal perfusion of sensory neurons with guanosine 5′- O-(2-thiodiphosphate) (GDP-β-S) via the recording pipette inhibited the sensitization produced by JTE-013 as well as prostaglandin E2. Pretreatment with pertussis toxin or the selective S1PR1 antagonist W146 blocked the sensitization produced by JTE-013. These results indicate that JTE-013 might act as an agonist at other G protein-coupled receptors. In neurons that were sensitized by JTE-013, single-cell RT-PCR studies demonstrated that these neurons did not express the mRNA for S1PR2. In behavioral studies, injection of JTE-013 into the rat's hindpaw produced a significant increase in the mechanical sensitivity in the ipsilateral, but not contralateral, paw. Injection of JTE-013 did not affect the withdrawal latency to thermal stimulation. Thus JTE-013 augments neuronal excitability independently of S1PR2 by unknown mechanisms that may involve activation of other G protein-coupled receptors such as S1PR1. Clearly, further studies are warranted to establish the causal nature of this increased sensitivity, and future studies of neuronal function using JTE-013 should be interpreted with caution.

scholarly journals Cholinergic microvillous cells in the mouse main olfactory epithelium and effect of acetylcholine on olfactory sensory neurons and supporting cells

2011 ◽  
Vol 106 (3) ◽  
pp. 1274-1287 ◽  
Author(s):  
Tatsuya Ogura ◽  
Steven A. Szebenyi ◽  
Kurt Krosnowski ◽  
Aaron Sathyanesan ◽  
Jacqueline Jackson ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Olfactory Epithelium ◽  
Transient Receptor Potential ◽  
Olfactory Sensory Neurons ◽  
Dependent Manner ◽  
Basal Cells ◽  
Supporting Cells ◽  
Concentration Dependent Manner ◽  
External Stimulation ◽  
Main Olfactory Epithelium

The mammalian olfactory epithelium is made up of ciliated olfactory sensory neurons (OSNs), supporting cells, basal cells, and microvillous cells. Previously, we reported that a population of nonneuronal microvillous cells expresses transient receptor potential channel M5 (TRPM5). Using transgenic mice and immunocytochemical labeling, we identify that these cells are cholinergic, expressing the signature markers of choline acetyltransferase (ChAT) and the vesicular acetylcholine transporter. This result suggests that acetylcholine (ACh) can be synthesized and released locally to modulate activities of neighboring supporting cells and OSNs. In Ca2+ imaging experiments, ACh induced increases in intracellular Ca2+ levels in 78% of isolated supporting cells tested in a concentration-dependent manner. Atropine, a muscarinic ACh receptor (mAChR) antagonist suppressed the ACh responses. In contrast, ACh did not induce or potentiate Ca2+ increases in OSNs. Instead ACh suppressed the Ca2+ increases induced by the adenylyl cyclase activator forskolin in some OSNs. Supporting these results, we found differential expression of mAChR subtypes in supporting cells and OSNs using subtype-specific antibodies against M1 through M5 mAChRs. Furthermore, we found that various chemicals, bacterial lysate, and cold saline induced Ca2+ increases in TRPM5/ChAT-expressing microvillous cells. Taken together, our data suggest that TRPM5/ChAT-expressing microvillous cells react to certain chemical or thermal stimuli and release ACh to modulate activities of neighboring supporting cells and OSNs via mAChRs. Our studies reveal an intrinsic and potentially potent mechanism linking external stimulation to cholinergic modulation of activities in the olfactory epithelium.

scholarly journals Roles of the ClC Chloride Channel CLH-1 in Food-associated Salt Chemotaxis Behavior of C. elegans

2020 ◽  
Author(s):  
Chanhyun Park ◽  
Yuki Sakurai ◽  
Hirofumi Sato ◽  
Shinji Kanda ◽  
Yuichi Iino ◽  
...  
Keyword(s):  
Salt Concentration ◽  
Chloride Channel ◽  
Ion Homeostasis ◽  
Sensory Information ◽  
Fluorescent Sensors ◽  
Neural Mechanisms ◽  
Anion Channels ◽  
C Elegans ◽  
Clc Chloride Channel ◽  
Navigation Strategies

AbstractThe ability of animals to process dynamic sensory information facilitates foraging in an ever changing environment. However, molecular and neural mechanisms underlying such ability remain elusive. The ClC anion channels/transporters play a pivotal role in cellular ion homeostasis across all phlya. Here we find a ClC chloride channel is involved in salt concentration chemotaxis of C. elegans. Genetic screening identified two altered-function mutations of clh-1 that disrupt experience-dependent salt chemotaxis. Using genetically encoded fluorescent sensors, we demonstrate that CLH-1 contributes to regulation of chloride and calcium dynamics of salt-sensing neuron, ASER. The mutant CLH-1 reduced responsiveness of ASER to salt stimuli in terms of both temporal resolution and intensity, which could disrupt navigation strategies for approaching preferred salt concentration. Furthermore, other ClC genes appeared to act redundantly in salt chemotaxis. These findings provide insights into the regulatory mechanism of neuronal responsivity by ClCs that contribute to modulation of navigation behavior.

scholarly journals Silver(i) ions modulate the stability of DNA duplexes containing cytosine, methylcytosine and hydroxymethylcytosine at different salt concentrations

RSC Advances ◽  
2015 ◽  
Vol 5 (4) ◽  
pp. 2655-2658 ◽  
Author(s):  
Yong Wang ◽  
Brandon Ritzo ◽  
Li-Qun Gu
Keyword(s):  
Salt Concentration ◽  
Dependent Manner ◽  
Dna Duplexes ◽  
Concentration Dependent Manner ◽  
The Stability

Ag(i) could modulate the stability of dsDNA which contains cytosine and cytosine modifications in a salt concentration dependent manner.

scholarly journals Neural integration underlying naturalistic prediction flexibly adapts to varying sensory input rate

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Thomas J. Baumgarten ◽  
Brian Maniscalco ◽  
Jennifer L. Lee ◽  
Matthew W. Flounders ◽  
Patrice Abry ◽  
...  
Keyword(s):  
Sensory Input ◽  
Sensory Information ◽  
Fixed Time ◽  
Neural Mechanisms ◽  
Natural Environments ◽  
Input Rate ◽  
Dynamic Stimuli ◽  
Neural Integration ◽  
Statistical Regularities ◽  
Natural Settings

AbstractPrediction of future sensory input based on past sensory information is essential for organisms to effectively adapt their behavior in dynamic environments. Humans successfully predict future stimuli in various natural settings. Yet, it remains elusive how the brain achieves effective prediction despite enormous variations in sensory input rate, which directly affect how fast sensory information can accumulate. We presented participants with acoustic sequences capturing temporal statistical regularities prevalent in nature and investigated neural mechanisms underlying predictive computation using MEG. By parametrically manipulating sequence presentation speed, we tested two hypotheses: neural prediction relies on integrating past sensory information over fixed time periods or fixed amounts of information. We demonstrate that across halved and doubled presentation speeds, predictive information in neural activity stems from integration over fixed amounts of information. Our findings reveal the neural mechanisms enabling humans to robustly predict dynamic stimuli in natural environments despite large sensory input rate variations.

The Anti-Atherogenic Properties of Sesamin are Mediated via Improved Macrophage Cholesterol Efflux Through PPARγ1-LXRα and MAPK Signaling

2014 ◽  
Vol 84 (1-2) ◽  
pp. 79-91 ◽  
Author(s):  
Amin F. Majdalawieh ◽  
Hyo-Sung Ro
Keyword(s):  
Cholesterol Efflux ◽  
Transcriptional Activity ◽  
Molecular Mechanisms ◽  
Foam Cell ◽  
Mapk Signaling ◽  
Luciferase Reporter ◽  
Foam Cell Formation ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Macrophage Cholesterol Efflux

Background: Foam cell formation resulting from disrupted macrophage cholesterol efflux, which is triggered by PPARγ1 and LXRα, is a hallmark of atherosclerosis. Sesamin and sesame oil exert anti-atherogenic effects in vivo. However, the exact molecular mechanisms underlying such effects are not fully understood. Aim: This study examines the potential effects of sesamin (0, 25, 50, 75, 100 μM) on PPARγ1 and LXRα expression and transcriptional activity as well as macrophage cholesterol efflux. Methods: PPARγ1 and LXRα expression and transcriptional activity are assessed by luciferase reporter assays. Macrophage cholesterol efflux is evaluated by ApoAI-specific cholesterol efflux assays. Results: The 50 μM, 75 μM, and 100 μM concentrations of sesamin up-regulated the expression of PPARγ1 (p< 0.001, p < 0.001, p < 0.001, respectively) and LXRα (p = 0.002, p < 0.001, p < 0.001, respectively) in a concentration-dependent manner. Moreover, 75 μM and 100 μM concentrations of sesamin led to 5.2-fold (p < 0.001) and 6.0-fold (p<0.001) increases in PPAR transcriptional activity and 3.9-fold (p< 0.001) and 4.2-fold (p < 0.001) increases in LXR transcriptional activity, respectively, in a concentration- and time-dependent manner via MAPK signaling. Consistently, 50 μM, 75 μM, and 100 μM concentrations of sesamin improved macrophage cholesterol efflux by 2.7-fold (p < 0.001), 4.2-fold (p < 0.001), and 4.2-fold (p < 0.001), respectively, via MAPK signaling. Conclusion: Our findings shed light on the molecular mechanism(s) underlying sesamin’s anti-atherogenic effects, which seem to be due, at least in part, to its ability to up-regulate PPARγ1 and LXRα expression and transcriptional activity, improving macrophage cholesterol efflux. We anticipate that sesamin may be used as a therapeutic agent for treating atherosclerosis.

Neutrophil Elastase Potentiates Cathepsin G-lnduced Platelet Activation

1992 ◽  
Vol 68 (05) ◽  
pp. 570-576 ◽  
Author(s):  
Mary A Selak
Keyword(s):  
Neutrophil Elastase ◽  
Cell Activation ◽  
Thromboxane A2 ◽  
Creatine Phosphate ◽  
Dense Granule ◽  
Cathepsin G ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Low Concentrations ◽  
High Concentrations

SummaryWe have previously demonstrated that human neutrophil cathepsin G is a strong platelet agonist that binds to a specific receptor. This work describes the effect of neutrophil elastase on cathepsin G-induced platelet responses. While platelets were not activated by high concentrations of neutrophil elastase by itself, elastase enhanced aggregation, secretion and calcium mobilization induced by low concentrations of cathepsin G. Platelet aggregation and secretion were potentiated in a concentration-dependent manner by neutrophil elastase with maximal responses observable at 200 nM. Enhancement was observed when elastase was preincubated with platelets for time intervals of 10–60 s prior to addition of a low concentration of cathepsin G and required catalytically-active elastase since phenylmethanesulphonyl fluoride-inhibited enzyme failed to potentiate cell activation. Neutrophil elastase potentiation of platelet responses induced by low concentrations of cathepsin G was markedly inhibited by creatine phosphate/creatine phosphokinase and/or indomethacin, indicating that the synergism between elastase and cathepsin G required the participation of ADP and thromboxane A2. On the other hand, platelet responses were not attenuated by the PAF antagonist BN 52021, signifying that PAF-acether did not play a role in elastase potentiation. At higher concentrations porcine pancreatic elastase exhibits similar effects to neutrophil elastase, demonstrating that the effect of elastase was not unique to the neutrophil protease. While neutrophil elastase failed to alter the ability of cathepsin G to hydrolyze a synthetic chromogenic substrate, preincubation of platelets with elastase increased the apparent affinity of cathepsin G binding to platelets. In contrast to their effect on cathepsin G-induced platelet responses, neither neutrophil nor pancreatic elasatse potentiated aggregation or dense granule release initiated by ADP, PAF-acether, arachidonic acid or U46619, a thromboxane A2 mimetic. Moreover, unlike its effect on cathepsin G, neutrophil elastase inhibited thrombin-induced responses. The current observations demonstrate that elastase can potentiate platelet responses mediated by low concentrations of cathepsin G, suggesting that both enzymes may function synergistically to activate platelets under conditions where neutrophil degranulation occurs.

Trimucytin: A Collagen-Like Aggregating Inducer Isolated from Trimeresurus mucrosquamatus Snake Venom

1993 ◽  
Vol 69 (03) ◽  
pp. 286-292 ◽  
Author(s):  
Che-Ming Teng ◽  
Feng-Nien Ko ◽  
Inn-Ho Tsai ◽  
Man-Ling Hung ◽  
Tur-Fu Huang
Keyword(s):  
Platelet Aggregation ◽  
Snake Venom ◽  
Inositol Phosphate ◽  
Shape Change ◽  
Platelet Activating Factor ◽  
Atp Release ◽  
Platelet Membrane ◽  
Thromboxane B2 ◽  
Dependent Manner ◽  
Concentration Dependent Manner

SummaryTrimucytin is a potent platelet aggregation inducer isolated from Trimeresurus mucrosquamatus snake venom. Similar to collagen, trimucytin has a run of (Gly-Pro-X) repeats at the N-terminal amino acids sequence. It induced platelet aggregation, ATP release and thromboxane formation in rabbit platelets in a concentration-dependent manner. The aggregation was not due to released ADP since it was not suppressed by creatine phosphate/creatine phosphokinase. It was not either due to thromboxane A2 formation because indomethacin and BW755C did not have any effect on the aggregation even thromboxane B2 formation was completely abolished by indomethacin. Platelet-activating factor (PAF) was not involved in the aggregation since a PAF antagonist, kadsurenone, did not affect. However, RGD-containing peptide triflavin inhibited the aggregation, but not the release of ATP, of platelets induced by trimucytin. Indomethacin, mepacrine, prostaglandin E1 and tetracaine inhibited the thromboxane B2 formation of platelets caused by collagen and trimucytin. Forskolin and sodium nitroprusside inhibited both platelet aggregation and ATP release, but not the shape change induced by trimucytin. In quin-2 loaded platelets, the rise of intracellular calcium concentration caused by trimucytin was decreased by 12-O-tetradecanoyl phorbol-13 acetate, imipramine, TMB-8 and indomethacin. In the absence of extracellular calcium, both collagen and trimucytin caused no thromboxane B2 formation, but still induced ATP release which was completely blocked by R 59022. Inositol phosphate formation in platelets was markedly enhanced by trimucytin and collagen. MAB1988, an antibody against platelet membrane glycoprotein Ia, inhibited trimucytinand collagen-induced platelet aggregation and ATP release. However, trimucytin did not replace the binding of 125I-labeled MAB1988 to platelets. Platelets pre-exposed to trimucytin were resistant to the second challenge with trimucytin itself or collagen. It is concluded that trimucytin may activate collagen receptors on platelet membrane, and cause aggregation and release mainly through phospholipase C-phosphoinositide pathway.

Influence of Brain Gangliosides on the Formation and Properties of Supported Lipid Bilayers for Binding Kinetics Studies

2018 ◽  
Author(s):  
Luke Jordan ◽  
Nathan Wittenberg
Keyword(s):  
Lipid Bilayers ◽  
Binding Kinetics ◽  
Supported Lipid Bilayers ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Supported Lipid Bilayer ◽  
Head Groups ◽  
Lipid Diffusion ◽  
Kinetics Of ◽  
Brain Gangliosides

This is a comprehensive study of the effects of the four major brain gangliosides (GM1, GD1b, GD1a, and GT1b) on the adsorption and rupture of phospholipid vesicles on SiO2 surfaces for the formation of supported lipid bilayer (SLB) membranes. Using quartz crystal microbalance with dissipation monitoring (QCM-D) we show that gangliosides GD1a and GT1b significantly slow the SLB formation process, whereas GM1 and GD1b have smaller effects. This is likely due to the net ganglioside charge as well as the positions of acidic sugar groups on ganglioside glycan head groups. Data is included that shows calcium can accelerate the formation of ganglioside-rich SLBs. Using fluorescence recovery after photobleaching (FRAP) we also show that the presence of gangliosides significantly reduces lipid diffusion coefficients in SLBs in a concentration-dependent manner. Finally, using QCM-D and GD1a-rich SLB membranes we measure the binding kinetics of an anti-GD1a antibody that has similarities to a monoclonal antibody that is a hallmark of a variant of Guillain-Barre syndrome.

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