Motor neuron M3 controls pharyngeal muscle relaxation timing in Caenorhabditis elegans

1. Previous work has shown that 12 of the 14 types of neurons in the Caenorhabditis elegans pharyngeal nervous system are collectively but not individually necessary for the trapping and transport of bacteria. The aim of these experiments was to determine the functions of individual neuron types by laser-killing combinations of neurons and looking at the effects on behavior. 2. The motor neuron M3 and the sensory neuron I5 are important in trapping bacteria, as shown by two observations. First, when M3 and I5 are both killed, trapping is inefficient in the isthmus (the middle section of the pharynx). Second, M3 is sufficient in the absence of the other 11 neuron types for normal trapping in the corpus (anterior pharynx). 3. M3 and I5 influence the timing of pharyngeal muscle motions. When M3 is killed, pump duration (the interval from the beginning of pharyngeal contraction to the end of relaxation) increases from 170 to 196 ms. This increase is at least partially due to a slower relaxation. Thus, M3 speeds up relaxation. Pump duration decreases to 159 ms when I5 is killed. When I5 and M3 are both killed, pump durations are long (192 ms), just as when M3 alone is killed. These observations, together with previous electron microscopic work showing synapses from I5 to M3, suggest that I5 slows down relaxation by inhibiting M3. 4. To explain these results, I propose that M3 and I5 promote bacterial trapping by regulating the relative timing of muscle relaxation in different regions of the pharynx.

Download Full-text

A Behavioral Survey of the Effects of Kavalactones on Caenorhabditis elegans Neuromuscular Transmission

Journal of Experimental Neuroscience ◽

10.1177/1179069517705384 ◽

2017 ◽

Vol 11 ◽

pp. 117906951770538 ◽

Cited By ~ 2

Author(s):

Bwarenaba B Kautu ◽

Juliana Phillips ◽

Kellie Steele ◽

M Shawn Mengarelli ◽

Eric A Nord

Keyword(s):

Nervous System ◽

Caenorhabditis Elegans ◽

Neuromuscular Transmission ◽

Plant Root ◽

Pacific Islanders ◽

The Other ◽

Aminobutyric Acid ◽

Major Constituent ◽

Root Extract ◽

Behavioral Assays

Kava is a plant root extract that is widely consumed by Pacific Islanders. Kava contains a class of lactone compounds called kavalactones. The sedative and anxiolytic effects of kava are likely attributed to the efficacies of kavalactones on the nervous system. Although some studies have implicated the potencies of certain kavalactone species on γ-aminobutyric acid transmission, evidence supporting the action of kavalactones on the eukaryotic neuromuscular junction (NMJ) and acetylcholine (ACh) transmission is scant. Here, we used behavioral assays to demonstrate the effects of kavalactones at the Caenorhabditis elegans NMJ. Our results suggest that kavalactones disrupt the inhibitory-excitatory balance at the NMJ. Such perturbation of NMJ activity is likely due to excess or prolonged ACh transmission. In addition, we found that kavain, a major constituent of kava, induced worm paralysis but not convulsions. Hence, the modulatory action of kavain could be distinct from the other kavalactone species.

Download Full-text

The genetics of feeding in Caenorhabditis elegans.

Genetics ◽

10.1093/genetics/133.4.897 ◽

1993 ◽

Vol 133 (4) ◽

pp. 897-917 ◽

Cited By ~ 26

Author(s):

L Avery

Keyword(s):

Nervous System ◽

Caenorhabditis Elegans ◽

Direct Evidence ◽

Muscle Membrane ◽

Excitable Cells ◽

Pharyngeal Muscle ◽

Genetic Mosaic ◽

Pharyngeal Muscles ◽

Pharmacological Studies ◽

Pha Genes

Abstract The pharynx of Caenorhabditis elegans is a nearly self-contained neuromuscular organ responsible for feeding. To identify genes involved in the development or function of the excitable cells of the pharynx, I screened for worms with visible defects in pharyngeal feeding behavior. Fifty-two mutations identified 35 genes, at least 22 previously unknown. The genes broke down into three broad classes: 2 pha genes, mutations in which caused defects in the shape of the pharynx, 7 phm genes, mutations in which caused defects in the contractile structures of the pharyngeal muscle, and 26 eat genes, mutants in which had abnormal pharyngeal muscle motions, but had normally shaped and normally birefringent pharynxes capable of vigorous contraction. Although the Eat phenotypes were diverse, most resembled those caused by defects in the pharyngeal nervous system. For some of the eat genes there is direct evidence from previous genetic mosaic and pharmacological studies that they do in fact affect nervous system. In eat-5 mutants the motions of the different parts of the pharynx were poorly synchronized. eat-6 and eat-12 mutants failed to relax their pharyngeal muscles properly. These pharyngeal motion defects are most easily explained as resulting from abnormal electrical excitability of the pharyngeal muscle membrane.

Download Full-text

ENU-3 is a novel outgrowth and guidance protein in c. elegans

10.32920/ryerson.14658099 ◽

2021 ◽

Author(s):

Callista Stephanie Yee

Keyword(s):

Amino Acids ◽

Nervous System ◽

Caenorhabditis Elegans ◽

Membrane Protein ◽

Motor Neuron ◽

Gene Product ◽

Motor Neurons ◽

Growth Cones ◽

C Elegans ◽

Extracellular Molecules

During the development of the nervous system, the migration of many cells and axons is guided by extracellular molecules. These molecules bind to receptors at the tips of the growth cones of migrating axons and trigger intracellular signalling to steer the axons along the correct trajectories. Previous work has identified a novel mutant, enu-3 (enhancer of Unc), that enhances the motor neuron axon outgrowth defects observed in strains of Caenorhabditis elegans that lack either the UNC-5 receptor or its ligand UNC-6/Netrin, enu-3 single mutants have weak motor neuron axon migration defects. Both outgrowth defects of double mutants and axon migration defects of enu-3 mutants were rescued by expression of the H04D03.1 gene product. Enu-3/H04D03.1 encodes a novel predicted putative trans-membrane protein of 204 amino acids. ENU-3 is expressed weakly expressed in many cell bodies along the ventral cord, including those of the DA and DB motor neurons.

Download Full-text

Analysis of the NK2 homeobox gene ceh-24 reveals sublateral motor neuron control of left-right turning during sleep

eLife ◽

10.7554/elife.24846 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 3

Author(s):

Juliane Schwarz ◽

Henrik Bringmann

Keyword(s):

Nervous System ◽

Caenorhabditis Elegans ◽

Motor Neuron ◽

Motor Neurons ◽

Three Dimensional ◽

Homeobox Gene ◽

Longitudinal Axis ◽

Neural Substrates ◽

Turning Behavior ◽

Cholinergic Function

Sleep is a behavior that is found in all animals that have a nervous system and that have been studied carefully. In Caenorhabditis elegans larvae, sleep is associated with a turning behavior, called flipping, in which animals rotate 180° about their longitudinal axis. However, the molecular and neural substrates of this enigmatic behavior are not known. Here, we identified the conserved NK-2 homeobox gene ceh-24 to be crucially required for flipping. ceh-24 is required for the formation of processes and for cholinergic function of sublateral motor neurons, which separately innervate the four body muscle quadrants. Knockdown of cholinergic function in a subset of these sublateral neurons, the SIAs, abolishes flipping. The SIAs depolarize during flipping and their optogenetic activation induces flipping in a fraction of events. Thus, we identified the sublateral SIA neurons to control the three-dimensional movements of flipping. These neurons may also control other types of motion.

Download Full-text

ENU-3 is a novel outgrowth and guidance protein in c. elegans

10.32920/ryerson.14658099.v1 ◽

2021 ◽

Author(s):

Callista Stephanie Yee

Keyword(s):

Amino Acids ◽

Nervous System ◽

Caenorhabditis Elegans ◽

Membrane Protein ◽

Motor Neuron ◽

Gene Product ◽

Motor Neurons ◽

Growth Cones ◽

C Elegans ◽

Extracellular Molecules

Download Full-text

Serial thin sectioning for pre- and post-embedding immunohistochemistry: Achieving consistent and reliable results for a 3-D reconstruction

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010014748x ◽

1993 ◽

Vol 51 ◽

pp. 328-329

Author(s):

Antonia M. Milroy

Keyword(s):

Nervous System ◽

Computer Assisted ◽

Serial Sectioning ◽

Electron Microscopic ◽

High Quality ◽

New Techniques ◽

3 Dimensional ◽

Multiple User ◽

Thin Sectioning ◽

Subcellular Level

In recent years many new techniques and instruments for 3-Dimensional visualization of electron microscopic images have become available. Higher accelerating voltage through thicker sections, photographed at a tilt for stereo viewing, or the use of confocal microscopy, help to analyze biological material without the necessity of serial sectioning. However, when determining the presence of neurotransmitter receptors or biochemical substances present within the nervous system, the need for good serial sectioning (Fig. 1+2) remains. The advent of computer assisted reconstruction and the possibility of feeding information from the specimen viewing chamber directly into a computer via a camera mounted on the electron microscope column, facilitates serial analysis. Detailed information observed at the subcellular level is more precise and extensive and the complexities of interactions within the nervous system can be further elucidated.We emphasize that serial ultra thin sectioning can be performed routinely and consistently in multiple user electron microscopy laboratories. Initial tissue fixation and embedding must be of high quality.

Download Full-text

Maternal-effect lethal mutations on linkage group II of Caenorhabditis elegans.

Genetics ◽

10.1093/genetics/120.4.977 ◽

1988 ◽

Vol 120 (4) ◽

pp. 977-986

Author(s):

K J Kemphues ◽

M Kusch ◽

N Wolf

Keyword(s):

Caenorhabditis Elegans ◽

Linkage Group ◽

Maternal Effect ◽

Essential Genes ◽

The Other ◽

C Elegans ◽

Lethal Mutations ◽

Embryonic Lethal ◽

Embryonic Lethal Mutations ◽

F1 Progeny

Abstract We have analyzed a set of linkage group (LG) II maternal-effect lethal mutations in Caenorhabditis elegans isolated by a new screening procedure. Screens of 12,455 F1 progeny from mutagenized adults resulted in the recovery of 54 maternal-effect lethal mutations identifying 29 genes. Of the 54 mutations, 39 are strict maternal-effect mutations defining 17 genes. These 17 genes fall into two classes distinguished by frequency of mutation to strict maternal-effect lethality. The smaller class, comprised of four genes, mutated to strict maternal-effect lethality at a frequency close to 5 X 10(-4), a rate typical of essential genes in C. elegans. Two of these genes are expressed during oogenesis and required exclusively for embryogenesis (pure maternal genes), one appears to be required specifically for meiosis, and the fourth has a more complex pattern of expression. The other 13 genes were represented by only one or two strict maternal alleles each. Two of these are identical genes previously identified by nonmaternal embryonic lethal mutations. We interpret our results to mean that although many C. elegans genes can mutate to strict maternal-effect lethality, most genes mutate to that phenotype rarely. Pure maternal genes, however, are among a smaller class of genes that mutate to maternal-effect lethality at typical rates. If our interpretation is correct, we are near saturation for pure maternal genes in the region of LG II balanced by mnC1. We conclude that the number of pure maternal genes in C. elegans is small, being probably not much higher than 12.

Download Full-text

ML-23 The outcome of malignant lymphoma of the central nervous system in a single institution

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa143.079 ◽

2020 ◽

Vol 2 (Supplement_3) ◽

pp. ii18-ii18

Author(s):

Kiyonori Kuwahara ◽

Shigeo Ohba ◽

Kazuyasu Matsumura ◽

Saeko Higashiguchi ◽

Daijiro Kojima ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Adverse Events ◽

Malignant Lymphoma ◽

Survival Time ◽

Progression Free Survival ◽

Treatment Method ◽

The Other ◽

High Dose ◽

Other Hand

Abstract Background: Although high dose-methotrexate therapy has been performed for primary central nervous system malignant lymphoma (PCNSL), R-MPV (rituximab, methotrexate (MTX), procarbazine and vincristine) therapy is currently the first line therapy for (PCNSL) in our hospital. This study examines the results of R-MPV therapy comparing with past treatment. Method/Subjects: Thirty-seven patients treated at our hospital from 2009 to 2020 were included. Overall survival time, progression free survival time, and toxicities were evaluated. Results: The average age of patients was 65.7 years. Patients included 21 males and 16 females. Thirty-six patients were diagnosed DLBCL by resected brain tumor tissues, and one was diagnosed DLBCL by vitreous biopsy. As initial treatment, rituximab±HD-MTX therapy (R±MTX group) was performed in 20 cases, HD-MTX therapy plus radiation (R±MTX+RT group) was performed in 12 cases, and RMPV therapy was performed in 5 cases (R-MPV group). Median OS of all cases was 69 months and median PFS was 38 months. Median OS was 69 months in R±MTX group and could not be calculated in R±MTX+RT, and R-MPV groups. Median PFS was 16 months and 56 months in R±MTX group and R±MTX+RT, respectively, and could not be calculated in the R-MPV group. Although the R-MPV group had a short follow-up period, the results were considered to be comparable to those of the R±MTX+RT group. On the other hand, grade 3/4 adverse events occurred in 50%, 25%, and 100%, respectively. Conclusion: R-MPV therapy may delay the timing of radiation and reduce the amount of radiation. On the other hand, the frequency of adverse events is high, and more strict management of treatment is required.

Download Full-text

Role of Autonomic Nervous System in Maintenance of Cerebral and Renal Hypertension

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1957.188.2.371 ◽

1957 ◽

Vol 188 (2) ◽

pp. 371-374 ◽

Cited By ~ 2

Author(s):

Sol Rothman ◽

Douglas R. Drury

Keyword(s):

Blood Pressure ◽

Nervous System ◽

Autonomic Nervous System ◽

Renal Hypertension ◽

The Other ◽

Peripheral Vasculature ◽

Blood Pressures ◽

Sympathetic Nervous ◽

Blood Pressure Responses

The blood pressure responses to various drugs were investigated in renal hypertensive, cerebral hypertensive and normotensive rabbits. Hexamethonium bromide and Dibenamine reduced the blood pressures of renal and cerebral hypertensives. Effects in the normal were insignificant. The cerebral hypertensive's blood pressure was slightly affected by benzodioxane. Blood pressure was not reduced at all in the other groups. Blood pressure of the renal hypertensive rabbit was greatly reduced by Veriloid and dihydroergocornine. Blood pressures of cerebral and normal animals were affected to a lesser degree. The results suggest that maintenance of hypertension in the cerebral hypertensive rabbit depends on an overactive sympathetic nervous system, possibly due to the release of medullary pressor centers from inhibitory impulses originating in higher centers; whereas, the maintenance of hypertension in the renal hypertensive rabbit may be attributed to an increased reactivity of the peripheral vasculature to a normal sympathetic tone.

Download Full-text

THE MOLECULAR ORGANIZATION OF HUMAN ALPHA 2-MACROGLOBULIN. AN IMMUNO ELECTRON MICROSCOPIC STUDY WITH MONOCLONAL ANTIBODIES

10.1055/s-0038-1643864 ◽

1987 ◽

Author(s):

E Delain ◽

M Barrav ◽

J Tapon-Bretaudière ◽

F Pochon ◽

F Van Leuven

Keyword(s):

Monoclonal Antibodies ◽

Binding Sites ◽

Divalent Cations ◽

The Other ◽

Molecular Organization ◽

Cellular Receptor ◽

Electron Microscopic ◽

Microscopic Method ◽

Bait Region ◽

Electron Microscopic Method

Electron microscopy is a very convenient method to localize the epitopes of monoclonal antibodies (mAbs) at the surface of macromolecules for studying their tree-dimensional organization.We applied this immuno-electron microscopic method to human ct2-macroglobulin (ct2M). 29 anti-α2M mAbs have been tested with the four different forms of a2M : native and chymotrypsin-transformed tetramers, and the corresponding dimers, obtained by dissociation with divalent cations. These mAbs can be classified in three types : those which are specific for 1) the H-like transformed molecules, 2) the native molecules, and 3) those which can react with both forms of α2M.1) Among the H-like α2M specific mAbs, several react with the 20 kD-domain which is recognized by the cellular receptor of transformed a2M. This domain is located at the carboxyterminal end of each monomer. One IgG binds to the end of two adjacent tips of the H-like form.The other mAbs of this type bind to the α2M tips at non-terminal positions. Intermolecular connections built polymers of alternating α2M and IgG molecules.2) Among the native a2M-specific mAbs some are able to inhibit the protease-induced transformation of the native α2M. The binding sites of these mAbs are demonstrated on the native half-molecules. One of these mAbs was also able to react with transformed dimers, in a region corresponding very likely to an inaccessible epitope in the tetrameric transformed α2M molecule.3) Among the mAbs of this type, only two were able to inhibit the protease-induced transformation of α2M. Obviously, their epitopes should be close to the bait region of α2M. The other mAbs reacting with both α2M forms did not inhibit the α2M transformation.All these mAbs can be distinguished by the structure of the immune complexes formed with all forms of α2M. The epitopes are more easily located on the dimers and on the H-like transformed α2M than on the native molecules.From these observations, we propose a new model of the tree-dimensional organization of the human α2M in its native and transformed configurations, and of its protease-induced transformation.

Download Full-text