scholarly journals Novel Strategies for Glutamate Clearance in the Glia-Deprived Synaptic Hub of C. elegans

2019 ◽  
Author(s):  
Joyce Chan ◽  
Kirsten KyungHwa Lee ◽  
Jenny Chan Ying Wong ◽  
Paola Morocho ◽  
Itzhak Mano
Keyword(s):  
Nervous System ◽  
Extracellular Space ◽  
Neuronal Morphology ◽  
Synaptic Activity ◽  
Neuronal Circuits ◽  
C Elegans ◽  
Synaptic Physiology ◽  
Classical Localization ◽  
Neuronal Systems ◽  
Neuronal Physiology

AbstractBrain function requires the ability to form neuronal circuits that mediate focused and accurate communication. Since the vast majority of brain synapses use Glutamate (Glu) as their neurotransmitter, unintended spillover of Glu between adjacent synapses is a critical challenge. To ensure accurate neurotransmission and avert synaptic mix-up, specialized Glu Transporters (GluTs) clear the synapse of released Glu. While classical views of neuronal morphology and physiology depict isolated spiny synapses enwrapped by GluT-expressing glia, in reality, a considerable portion of synapses are flat, glial coverage in some parts of the brain is rather sparse, and extracellular space is larger than previously estimated. This suggests that diffusion in interstitial fluids might have an important role in Glu clearance in these synapses. To understand basic principles of Glu clearance in flat-, glia-deprived synapses, we study the physiology of neuronal circuits in the C. elegans nerve ring, the nematode’s aspiny synaptic hub. We use behavioral assays, Ca2+ imaging, and iGluSnFR to follow synaptic activity in intact animals. We find that synapses in a nociceptive avoidance circuit are dramatically affected by distal GluTs, while an adjacent chemoattraction circuit is controlled by proximal GluTs. We also find that pharyngeal pulsatility and mobility, which could agitate interstitial fluids, are critical for synaptic physiology. We therefore conclude that robust Glu clearance in the nematode is provided differentially by distal and proximal GluTs, aided by agitation of interstitial fluids. Such principles might be informative in determining additional factors that contribute to robust Glu clearance in other neuronal systems.Significance StatementThe nervous system depends on faithful relay of information without inadvertent mixing of signals between neuronal circuits. Classical views of the nervous system depict isolated synapses, enwrapped by glia that express neurotransmitter-transporters. However, this view is incomplete, since many synapses are flat, deprived of glia, and exposed to a larger-than-expected extracellular space. We use optogenetic tools to investigate glutamate clearance strategies in the aspiny and glia-deprived synaptic hub of intact nematodes. We find a division of labor among Glutamate transporters: while some transporters display classical localization near the synapses, others are distal, and cooperate with agitation of interstitial fluids to prevent glutamate accumulation. These novel principles might contribute to synaptic clearance in higher animals, affecting normal neuronal physiology and disease.

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

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.

Ancestral roles of glia suggested by the nervous system of Caenorhabditis elegans

2007 ◽  
Vol 3 (1) ◽  
pp. 55-61 ◽  
Author(s):  
Maxwell G. Heiman ◽  
Shai Shaham
Keyword(s):  
Nervous System ◽  
Caenorhabditis Elegans ◽  
Glial Cell ◽  
Glial Cells ◽  
Cell Types ◽  
Neuronal Morphology ◽  
Sensory Organs ◽  
Nematode Caenorhabditis Elegans ◽  
C Elegans

AbstractThe nematode Caenorhabditis elegans has a simple nervous system with glia restricted primarily to sensory organs. Some of the activities that would be provided by glia in the mammalian nervous system are either absent or provided by non-glial cell types in C. elegans, with only a select set of mammalian glial activities being similarly provided by specialized glial cells in this animal. These observations suggest that ancestral roles of glia may be to modulate neuronal morphology and neuronal sensitivity in sensory organs.

scholarly journals Semaphorin signaling restricts neuronal regeneration in C. elegans

2021 ◽  
Author(s):  
Maria Belen Harreguy ◽  
Esha Shah ◽  
Zainab Tanvir ◽  
Blandine Simprevil ◽  
Tracy S. Tran ◽  
...  
Keyword(s):  
Nervous System ◽  
Synapse Formation ◽  
Neuronal Morphology ◽  
Axonal Guidance ◽  
Axon Pathfinding ◽  
Neuronal Regeneration ◽  
C Elegans ◽  
Locomotion Behavior ◽  
Neuronal Growth Cone ◽  
Knockout Animals

Extracellular signaling proteins serve as neuronal growth cone guidance molecules during development and are well positioned to be involved in neuronal regeneration and recovery from injury. Semaphorins and their receptors, the plexins, are a family of conserved proteins involved in development that, in the nervous system, are axonal guidance cues mediating axon pathfinding and synapse formation. The Caenorhabditis elegans genome encodes for three semaphorins and two plexin receptors: the transmembrane semaphorins, SMP-1 and SMP-2, signal through their receptor, PLX-1, while the secreted semaphorin, MAB-20, signals through PLX-2. Here, we determined the neuronal morphology and locomotion behavior of knockout animals missing each of the semaphorins and plexins; we described the expression pattern of all plexins in the nervous system of C. elegans; and we evaluated their effect on the regeneration of motoneuron neurites and the recovery of locomotion behavior following precise laser microsurgery.

Behavioral Effects of Volatile Anesthetics in Caenorhabditis elegans

1996 ◽  
Vol 85 (4) ◽  
pp. 901-912 ◽  
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.

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

BMC Genomics ◽  
2008 ◽  
Vol 9 (1) ◽  
Author(s):  
Joseph D Watson ◽  
Shenglong Wang ◽  
Stephen E Von Stetina ◽  
W Clay Spencer ◽  
Shawn Levy ◽  
...  
Keyword(s):  
Nervous System ◽  
Rna Amplification ◽  
C Elegans

Identification of two types of synaptic activity in the earthworm nervous system during locomotion

Neuroscience ◽  
2003 ◽  
Vol 121 (2) ◽  
pp. 473-478 ◽  
Author(s):  
K Mizutani ◽  
T Shimoi ◽  
Y Kitamura ◽  
H Ogawa ◽  
K Oka
Keyword(s):  
Nervous System ◽  
Synaptic Activity

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

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?

scholarly journals Extended Synaptotagmin is a presynaptic ER Ca2+ sensor that promotes neurotransmission and synaptic growth in Drosophila

2017 ◽  
Author(s):  
Koto Kikuma ◽  
Daniel Kim ◽  
David Sutter ◽  
Xiling Li ◽  
Dion K. Dickman
Keyword(s):  
Plasma Membrane ◽  
Membrane Trafficking ◽  
Synaptic Activity ◽  
Synaptic Growth ◽  
Synaptic Physiology ◽  
Lipid Exchange ◽  
Membrane Tethering ◽  
Conserved Gene ◽  
Neuronal Functions

ABSTRACTThe endoplasmic reticulum (ER) is an extensive presynaptic organelle, exerting important influences at synapses by responding to Ca2+ and modulating transmission, growth, lipid metabolism, and membrane trafficking. Despite intriguing evidence for these crucial functions, how presynaptic ER influences synaptic physiology remains enigmatic. To gain insight into this question, we have generated and characterized mutations in the single Extended Synaptotagmin (Esyt) ortholog in Drosophila. Esyts are evolutionarily conserved ER proteins with Ca2+ sensing domains that have recently been shown to orchestrate membrane tethering and lipid exchange between the ER and plasma membrane. We first demonstrate that Esyt localizes to an extensive ER structure that invades presynaptic terminals at the neuromuscular junction. Next, we show that synaptic growth, structure, function, and plasticity are surprisingly unperturbed at synapses lacking Esyt expression. However, presynaptic overexpression of Esyt leads to enhanced synaptic growth, neurotransmission, and sustainment of the vesicle pool during intense levels of activity, suggesting that elevated Esyt at the ER promotes constitutive membrane trafficking or lipid exchange with the plasma membrane. Finally, we find that Esyt mutants fail to maintain basal neurotransmission and short term plasticity at elevated extracellular Ca2+, consistent with Esyt functioning as an ER Ca2+ sensor that modulates synaptic activity. Thus, we identify Esyt as a presynaptic ER Ca2+ sensor that can promote neurotransmission and synaptic growth, revealing the first in vivo neuronal functions of this conserved gene family.

scholarly journals Functional connectomics from neural dynamics: probabilistic graphical models for neuronal network of Caenorhabditis elegans

2018 ◽  
Vol 373 (1758) ◽  
pp. 20170377 ◽  
Author(s):  
Hexuan Liu ◽  
Jimin Kim ◽  
Eli Shlizerman
Keyword(s):  
Time Series ◽  
Nervous System ◽  
Caenorhabditis Elegans ◽  
Graphical Models ◽  
Neuronal Network ◽  
Graphical Model ◽  
Time Series Data ◽  
Series Data ◽  
Neuronal Responses ◽  
C Elegans

We propose an approach to represent neuronal network dynamics as a probabilistic graphical model (PGM). To construct the PGM, we collect time series of neuronal responses produced by the neuronal network and use singular value decomposition to obtain a low-dimensional projection of the time-series data. We then extract dominant patterns from the projections to get pairwise dependency information and create a graphical model for the full network. The outcome model is a functional connectome that captures how stimuli propagate through the network and thus represents causal dependencies between neurons and stimuli. We apply our methodology to a model of the Caenorhabditis elegans somatic nervous system to validate and show an example of our approach. The structure and dynamics of the C. elegans nervous system are well studied and a model that generates neuronal responses is available. The resulting PGM enables us to obtain and verify underlying neuronal pathways for known behavioural scenarios and detect possible pathways for novel scenarios. This article is part of a discussion meeting issue ‘Connectome to behaviour: modelling C. elegans at cellular resolution’.

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