scholarly journals A wake-active locomotion circuit depolarizes a sleep-active neuron to switch on sleep

2019 ◽  
Author(s):  
Elisabeth Maluck ◽  
Inka Busack ◽  
Judith Besseling ◽  
Florentin Masurat ◽  
Michal Turek ◽  
...  
Keyword(s):  
Active Sleep ◽  
Sleep State ◽  
Developmentally Regulated ◽  
Active Neuron ◽  
Flip Flop ◽  
C Elegans ◽  
State Switching ◽  
Locomotion Behavior ◽  
Forward Locomotion ◽  
Separate Activation

AbstractSleep-active neurons depolarize during sleep to suppress wakefulness circuits. Wake-active wake-promoting neurons in turn shut down sleep-active neurons, thus forming a bipartite flip-flop switch. However, how sleep is switched on is unclear because it is not known how wakefulness is translated into sleep-active neuron depolarization when the system is set to sleep. Using optogenetics in C. elegans, we solved the presynaptic circuit for depolarization of the sleep-active RIS neuron during developmentally-regulated sleep, also known as lethargus. Surprisingly, we found that RIS activation requires neurons that have known roles in wakefulness and locomotion behavior. The RIM interneurons, which are active during and can induce reverse locomotion, play a complex role and can act as inhibitors of RIS when they are strongly depolarized and as activators of RIS when they are modestly depolarized. The PVC command interneurons, which are known to promote forward locomotion during wakefulness, act as major activators of RIS. The properties of these locomotion neurons are modulated during lethargus. The RIMs become less excitable. The PVCs become resistant to inhibition and have an increased capacity to activate RIS. Separate activation of neither the PVCs nor the RIMs appears to be sufficient for sleep induction; instead, our data suggests that they act in concert to activate RIS. Forward and reverse circuit activity is normally mutually exclusive. Our data suggest that RIS may be activated at the transition between forward and reverse locomotion states, perhaps when both reverse (including RIM) and forward (PVC) circuit activity overlaps. While RIS is not strongly activated outside of lethargus, altered activity of the locomotion interneurons during lethargus favors strong RIS activation and thus sleep. The control of sleep-active neurons by locomotion circuits suggests that sleep may have evolved from locomotion quiescence. The flip-flop sleep switch in C. elegans thus requires an additional component, wake-active sleep-promoting neurons that translate wakefulness into the depolarization of a sleep-active neuron when the worm is sleepy. Wake-active sleep-promoting circuits may also be required for sleep state switching in other animals including in mammals.

scholarly journals A quiescent state following mild sensory arousal in Caenorhabditis elegans is potentiated by stress

2019 ◽  
Author(s):  
Patrick D. McClanahan ◽  
Jessica M. Dubuque ◽  
Daphne Kontogiorgos-Heintz ◽  
Ben F. Habermeyer ◽  
Joyce H. Xu ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Light Exposure ◽  
Light Stimulus ◽  
Low Frequency ◽  
Behavioral Responses ◽  
Quiescent State ◽  
Sleep State ◽  
C Elegans ◽  
Epidermal Growth ◽  
Cellular Stressors

AbstractAn animal’s behavioral and physiological response to stressors includes changes to its responses to stimuli. How such changes occur is not well understood. Here we describe a Caenorhabditis elegans quiescent behavior, post-response quiescence (PRQ), which is modulated by the C. elegans response to cellular stressors. Following an aversive mechanical or blue light stimulus, worms respond first by briefly moving, and then become more quiescent for a period lasting tens of seconds. PRQ occurs at low frequency in unstressed animals, but is more frequent in animals that have experienced cellular stress due to ultraviolet light exposure as well as in animals following overexpression of epidermal growth factor (EGF). PRQ requires the function of the carboxypeptidase EGL-21 and the calcium-activated protein for secretion (CAPS) UNC-31, suggesting it has a neuropeptidergic mechanism. Although PRQ requires the sleep-promoting neurons RIS and ALA, it is not accompanied by decreased arousability, and does not appear to be homeostatically regulated, suggesting that it is not a sleep state. PRQ represents a simple, tractable model for studying how neuromodulatory states like stress alter behavioral responses to stimuli.

scholarly journals The Caenorhabditis elegans homologue of the extracellular calcium binding protein SPARC/osteonectin affects nematode body morphology and mobility.

1993 ◽  
Vol 4 (9) ◽  
pp. 941-952 ◽  
Author(s):  
J E Schwarzbauer ◽  
C S Spencer
Keyword(s):  
Extracellular Matrix ◽  
Caenorhabditis Elegans ◽  
Calcium Binding ◽  
Fusion Gene ◽  
Muscle Cells ◽  
Gene Organization ◽  
The Body ◽  
Matrix Assembly ◽  
Developmentally Regulated ◽  
C Elegans

The extracellular matrix-associated protein, SPARC (osteonectin [Secreted Protein Acidic and Rich in Cysteine]), modulates cell adhesion and induces a change in cell morphology. SPARC expression in mammals is developmentally regulated and is highest at sites of extracellular matrix assembly and remodeling such as parietal endoderm and bone. We have isolated cDNA and genomic DNA clones encoding the Caenorhabditis elegans homologue of SPARC. The gene organization is highly conserved, and the proteins encoded by mouse, human, and nematode genes are about 38% identical. SPARC consists of four domains (I-IV) based on predicted secondary structure. Using bacterial fusion proteins containing nematode domain I or the domain IV EF-hand motif, we show that, like the mammalian proteins, both domains bind calcium. In transgenic nematodes expressing a SPARC-lacZ fusion gene, beta-galactosidase staining accumulated in a striated pattern in the more heavily stained muscle cells along the body. Comparison of the pattern of transgene expression to unc-54-lacZ animals demonstrated that SPARC is expressed by body wall and sex muscle cells. Appropriate levels of SPARC are essential for normal C. elegans development and muscle function. Transgenic nematodes overexpressing the wild-type SPARC gene were abnormal. Embryos were deformed, and adult hermaphrodites had vulval protrusions and an uncoordinated (Unc) phenotype with reduced mobility and paralysis.

scholarly journals The Nc1/Endostatin Domain of Caenorhabditis elegans Type Xviii Collagen Affects Cell Migration and Axon Guidance

2001 ◽  
Vol 152 (6) ◽  
pp. 1219-1232 ◽  
Author(s):  
Brian D. Ackley ◽  
Jennifer R. Crew ◽  
Harri Elamaa ◽  
Tania Pihlajaniemi ◽  
Calvin J. Kuo ◽  
...  
Keyword(s):  
Cell Migration ◽  
Caenorhabditis Elegans ◽  
Axon Guidance ◽  
Ectopic Expression ◽  
Basement Membranes ◽  
Protein Isoforms ◽  
Developmentally Regulated ◽  
C Elegans ◽  
Collagen Xviii ◽  
Nc1 Domain

Type XVIII collagen is a homotrimeric basement membrane molecule of unknown function, whose COOH-terminal NC1 domain contains endostatin (ES), a potent antiangiogenic agent. The Caenorhabditis elegans collagen XVIII homologue, cle-1, encodes three developmentally regulated protein isoforms expressed predominantly in neurons. The CLE-1 protein is found in low amounts in all basement membranes but accumulates at high levels in the nervous system. Deletion of the cle-1 NC1 domain results in viable fertile animals that display multiple cell migration and axon guidance defects. Particular defects can be rescued by ectopic expression of the NC1 domain, which is shown to be capable of forming trimers. In contrast, expression of monomeric ES does not rescue but dominantly causes cell and axon migration defects that phenocopy the NC1 deletion, suggesting that ES inhibits the promigratory activity of the NC1 domain. These results indicate that the cle-1 NC1/ES domain regulates cell and axon migrations in C. elegans.

scholarly journals Proprioceptive Coupling within Motor Neurons Drives C. elegans Forward Locomotion

Neuron ◽  
2012 ◽  
Vol 76 (4) ◽  
pp. 750-761 ◽  
Author(s):  
Quan Wen ◽  
Michelle D. Po ◽  
Elizabeth Hulme ◽  
Sway Chen ◽  
Xinyu Liu ◽  
...  
Keyword(s):  
Motor Neurons ◽  
C Elegans ◽  
Forward Locomotion

scholarly journals Postnatal maturation of laryngeal chemoreflexes in the preterm lamb

2007 ◽  
Vol 102 (4) ◽  
pp. 1429-1438 ◽  
Author(s):  
Marie St-Hilaire ◽  
Nathalie Samson ◽  
Elise Nsegbe ◽  
Charles Duvareille ◽  
François Moreau-Bussière ◽  
...  
Keyword(s):  
Heart Rate ◽  
Lower Airway ◽  
Distilled Water ◽  
Active Sleep ◽  
Sleep State ◽  
Quiet Sleep ◽  
General Belief ◽  
Postnatal Maturation ◽  
Laryngeal Mucosa ◽  
Life Threatening

Laryngeal chemoreflexes (LCR) are triggered by the contact of liquids with the laryngeal mucosa. In the mature organism, LCR trigger lower airway protective responses (coughing, effective swallowing, and arousal) to prevent aspiration. General belief holds that LCR are responsible for apnea and bradycardia in the newborn mammal, including humans. Our laboratory has recently shown that LCR in full-term lambs are consistently analogous to the mature LCR reported in adult mammals, without significant apneas and bradycardias (St-Hilaire M, Nsegbe E, Gagnon-Gervais K, Samson N, Moreau-Bussiere F, Fortier PH, and Praud J-P. J Appl Physiol 98: 2197–2203, 2005). The aim of the present study was to assess LCR in nonsedated, newborn preterm lambs born at 132 days of gestation (term = 147 days). The preterm lambs were instrumented for recording glottal adductor electromyogram, electroencephalogram, eye movements, heart rate, respiration, and oximetry. A chronic supraglottal catheter was used for injecting 0.5 ml of saline, distilled water, and HCl (pH 2) during quiet sleep, active sleep, and wakefulness on postnatal days 7 (D7) and 14 (D14). Laryngeal stimulation by water or HCl on D7 induced significant apneas, bradycardia, and desaturation, which, at times, appeared potentially life-threatening. No significant apneas, bradycardias, or desaturation were observed on D14. No consistent effects of sleep state could be shown in the present study. In conclusion, laryngeal stimulation by liquids triggers potentially dangerous LCR in preterm lambs on D7, but not on D14. It is proposed that maturation of the LCR between D7 and D14 is partly involved in the disappearance of apneas/bradycardias of prematurity with postnatal age.

scholarly journals Temporal and spatial expression patterns of the small heat shock (hsp16) genes in transgenic Caenorhabditis elegans.

1992 ◽  
Vol 3 (2) ◽  
pp. 221-233 ◽  
Author(s):  
E G Stringham ◽  
D K Dixon ◽  
D Jones ◽  
E P Candido
Keyword(s):  
Caenorhabditis Elegans ◽  
Heat Shock ◽  
Gene Pair ◽  
Expression Patterns ◽  
Developmentally Regulated ◽  
Noncoding Sequences ◽  
C Elegans ◽  
Gene Pairs ◽  
Temporal And Spatial ◽  
Beta Galactosidase

The expression of the hsp16 gene family in Caenorhabditis elegans has been examined by introducing hsp16-lacZ fusions into the nematode by transformation. Transcription of the hsp16-lacZ transgenes was totally heat-shock dependent and resulted in the rapid synthesis of detectable levels of beta-galactosidase. Although the two hsp16 gene pairs of C. elegans are highly similar within both their coding and noncoding sequences, quantitative and qualitative differences in the spatial pattern of expression between gene pairs were observed. The hsp16-48 promoter was shown to direct greater expression of beta-galactosidase in muscle and hypodermis, whereas the hsp16-41 promoter was more efficient in intestine and pharyngeal tissue. Transgenes that eliminated one promoter from a gene pair were expressed at reduced levels, particularly in postembryonic stages, suggesting that the heat shock elements in the intergenic region of an hsp16 gene pair may act cooperatively to achieve high levels of expression of both genes. Although the hsp16 gene pairs are never constitutively expressed, their heat inducibility is developmentally restricted; they are not heat inducible during gametogenesis or early embryogenesis. The hsp16 genes represent the first fully inducible system in C. elegans to be characterized in detail at the molecular level, and the promoters of these genes should find wide applicability in studies of tissue- and developmentally regulated genes in this experimental organism.

scholarly journals Distributed Rhythm Generators Underlie Caenorhabditis elegans Forward Locomotion

2017 ◽  
Author(s):  
Anthony D. Fouad ◽  
Shelly Teng ◽  
Julian R. Mark ◽  
Alice Liu ◽  
Pilar Alvarez-Illera ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Motor Neurons ◽  
Animal Behavior ◽  
Rhythm Generation ◽  
Rhythmic Movements ◽  
Neural Oscillators ◽  
Motor Circuit ◽  
C Elegans ◽  
Body Regions ◽  
Forward Locomotion

ABSTRACTCoordinated rhythmic movements are ubiquitous in animal behavior. In many organisms, chains of neural oscillators underlie the generation of these rhythms. In C. elegans, locomotor wave generation has been poorly understood; in particular, it is unclear where in the circuit rhythms are generated, and whether there exists more than one such generator. We used optogenetic and ablation experiments to probe the nature of rhythm generation in the locomotor circuit. We found that multiple sections of forward locomotor circuitry are capable of independently generating rhythms. By perturbing different components of the motor circuit, we localize the source of secondary rhythms to cholinergic motor neurons in the midbody. Using rhythmic optogenetic perturbation we demonstrate bidirectional entrainment of oscillations between different body regions. These results show that, as in many other vertebrates and invertebrates, the C. elegans motor circuit contains multiple oscillators that coordinate activity to generate behavior.

scholarly journals A neuromechanical model of multiple network rhythmic pattern generators for forward locomotion in C. elegans

2019 ◽  
Author(s):  
Erick Olivares ◽  
Eduardo J. Izquierdo ◽  
Randall D. Beer
Keyword(s):  
Nerve Cord ◽  
Ventral Nerve Cord ◽  
Stretch Receptor ◽  
Rhythmic Pattern ◽  
Pacemaker Neurons ◽  
C Elegans ◽  
Forward Locomotion ◽  
Pattern Generators ◽  
Multiple Network ◽  
A Chain

AbstractMultiple mechanisms contribute to the generation, propagation, and coordination of the rhythmic patterns necessary for locomotion in Caenorhabditis elegans. Current experiments have focused on two possibilities: pacemaker neurons and stretch-receptor feedback. Here, we focus on whether it is possible that a chain of multiple network rhythmic pattern generators in the ventral nerve cord also contribute to locomotion. We use a simulation model to search for electrophysiological parameters of the anatomically constrained ventral nerve cord circuit that, when embodied and situated, can drive forward locomotion on agar, in the absence of pacemaker neurons or stretch-receptor feedback. Systematic exploration of the space of possible solutions reveals that there are multiple configurations that result in locomotion that is consistent with certain aspects of the kinematics of worm locomotion on agar. Analysis of the best solutions reveals that gap junctions between different classes of motorneurons in the ventral nerve cord can play key roles in coordinating the multiple rhythmic pattern generators.

scholarly journals Cargo crowding, stationary clusters and dynamical reservoirs in axonal transport

2021 ◽  
Author(s):  
Vinod Kumar ◽  
Amruta Vasudevan ◽  
Keertana Venkatesh ◽  
Reshma Maiya ◽  
Parul Sood ◽  
...  
Keyword(s):  
Axonal Transport ◽  
Molecular Motors ◽  
Experimental System ◽  
C Elegans ◽  
On Demand ◽  
Motion State ◽  
State Switching ◽  
Cargo Transport ◽  
Functional Relevance

AbstractMolecular motors drive the directed transport of presynaptic vesicles along the narrow axons of nerve cells. Stationary clusters of such vesicles are a prominent feature of axonal transport, but little is known about their physiological and functional relevance. Here, we develop a simulation model describing key features of axonal cargo transport with a view to addressing this question, benchmarking the model against our experiments in the touch neurons of C. elegans. Our simulations provide for multiple microtubule tracks and varied cargo motion states while also incorporating cargo-cargo interactions. Our model also incorporates obstacles to vesicle transport in the form of microtubule ends, stalled vesicles, and stationary mitochondria. We devise computational methodologies to simulate both axonal bleaching and axotomy, showing that our results reproduce the properties of both moving as well as stationary cargo in vivo. Increasing vesicle numbers leads to larger and more long-lived stationary clusters of vesicular cargo. Vesicle clusters are dynamically stable, explaining why they are ubiquitously seen. Modulating the rates of cargo motion-state switching allows cluster lifetimes and flux to be tuned both in simulations and experiments. We demonstrate, both in simulations and in an experimental system, that suppressing reversals leads to larger stationary vesicle clusters being formed while also reducing flux. Our simulation results support the view that the physiological significance of clusters is located in their role as dynamic reservoirs of cargo vesicles, capable of being released or sequestered on demand.

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