scholarly journals C. elegans enteric motor neurons fire synchronized action potentials underlying the defecation motor program

2021 ◽  
Author(s):  
Jingyuan Jiang ◽  
Yifan Su ◽  
Rulin Zhang ◽  
Haiwen Li ◽  
Louis Tao ◽  
...  
Keyword(s):  
Nervous System ◽  
Motor Neurons ◽  
Action Potentials ◽  
Motor Program ◽  
Whole Body ◽  
Long Distance ◽  
C Elegans ◽  
Neural Imaging ◽  
Negative Spike ◽  
Behavior Tracking

The C. elegans nervous system was thought to be strictly analog, constituted solely by graded neurons. We recently discovered neuronal action potentials in the sensory neuron AWA; however, the extent to which the C. elegans nervous system relies on analog or digital neural signaling and coding is unclear. Here we report that the enteric motor neurons AVL and DVB fire all-or-none calcium-mediated action potentials that play essential roles in the rhythmic defecation behavior in C. elegans. Both AVL and DVB synchronously fire giant action potentials to faithfully execute all-or-none expulsion following the intestinal pacemaker. AVL fires unusual compound action potentials with each positive calcium-mediated spike followed by a potassium-mediated negative spike. The depolarizing calcium spikes in AVL are mediated by a CaV2 calcium channel UNC-2, while the negative potassium spikes are mediated by a repolarization-activated potassium channel EXP-2. Whole-body behavior tracking and simultaneous neural imaging in free-moving animals suggest that action potentials initiated in AVL in the head propagate along its axon to the tail and activate DVB through the INX-1 gap junction. Synchronized action potential spikes between AVL and DVB, as well as the negative spike and long-lasting afterhyperpolarization in AVL, play an important function in executing expulsion behavior. This work provides the first evidence that in addition to sensory coding, C. elegans motor neurons also use digital coding scheme to perform specific functions including long-distance communication and temporal synchronization, suggesting further, unforeseen electrophysiological diversity remains to be discovered in the C. elegans nervous system.

scholarly journals rab-27 acts in an intestinal pathway to inhibit axon regeneration in C. elegans

PLoS Genetics ◽  
2021 ◽  
Vol 17 (11) ◽  
pp. e1009877
Author(s):  
Alexander T. Lin-Moore ◽  
Motunrayo J. Oyeyemi ◽  
Marc Hammarlund
Keyword(s):  
Motor Neurons ◽  
Axon Regeneration ◽  
Rab Gtpase ◽  
Long Distance ◽  
Extrinsic Factors ◽  
C Elegans ◽  
Cellular Environment ◽  
Neuropeptide Secretion ◽  
Neuronal Tissues ◽  
Nervous System Function

Injured axons must regenerate to restore nervous system function, and regeneration is regulated in part by external factors from non-neuronal tissues. Many of these extrinsic factors act in the immediate cellular environment of the axon to promote or restrict regeneration, but the existence of long-distance signals regulating axon regeneration has not been clear. Here we show that the Rab GTPase rab-27 inhibits regeneration of GABAergic motor neurons in C. elegans through activity in the intestine. Re-expression of RAB-27, but not the closely related RAB-3, in the intestine of rab-27 mutant animals is sufficient to rescue normal regeneration. Several additional components of an intestinal neuropeptide secretion pathway also inhibit axon regeneration, including NPDC1/cab-1, SNAP25/aex-4, KPC3/aex-5, and the neuropeptide NLP-40, and re-expression of these genes in the intestine of mutant animals is sufficient to restore normal regeneration success. Additionally, NPDC1/cab-1 and SNAP25/aex-4 genetically interact with rab-27 in the context of axon regeneration inhibition. Together these data indicate that RAB-27-dependent neuropeptide secretion from the intestine inhibits axon regeneration, and point to distal tissues as potent extrinsic regulators of regeneration.

scholarly journals Reduced motoneuron excitability in a rat model of sepsis

2013 ◽  
Vol 109 (7) ◽  
pp. 1775-1781 ◽  
Author(s):  
Paul Nardelli ◽  
Jaffar Khan ◽  
Randall Powers ◽  
Tim C. Cope ◽  
Mark M. Rich
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Intensive Care ◽  
Motor Unit ◽  
Action Potentials ◽  
Cecal Ligation ◽  
Membrane Properties ◽  
Whole Body ◽  
Repetitive Firing ◽  
The Central Nervous System

Many critically ill patients in intensive care units suffer from an infection-induced whole body inflammatory state known as sepsis, which causes severe weakness in patients who survive. The mechanisms by which sepsis triggers intensive care unit-acquired weakness (ICUAW) remain unclear. Currently, research into ICUAW is focused on dysfunction of the peripheral nervous system. During electromyographic studies of patients with ICUAW, we noticed that recruitment was limited to few motor units, which fired at low rates. The reduction in motor unit rate modulation suggested that functional impairment within the central nervous system contributes to ICUAW. To understand better the mechanism underlying reduced firing motor unit firing rates, we moved to the rat cecal ligation and puncture model of sepsis. In isoflurane-anesthetized rats, we studied the response of spinal motoneurons to injected current to determine their capacity for initiating and firing action potentials repetitively. Properties of single action potentials and passive membrane properties of motoneurons from septic rats were normal, suggesting excitability was normal. However, motoneurons exhibited striking dysfunction during repetitive firing. The sustained firing that underlies normal motor unit activity and smooth force generation was slower, more erratic, and often intermittent in septic rats. Our data are the first to suggest that reduced excitability of neurons within the central nervous system may contribute to ICUAW.

scholarly journals cAMP controls a trafficking mechanism that directs the neuron specificity and subcellular placement of electrical synapses

2021 ◽  
Author(s):  
Sierra Palumbos ◽  
Rachel Skelton ◽  
Rebecca McWhirter ◽  
Amanda Mitchell ◽  
Isaiah Swann ◽  
...  
Keyword(s):  
Nervous System ◽  
Gap Junction ◽  
Motor Neurons ◽  
Live Cell Imaging ◽  
Cell Imaging ◽  
Electrical Synapse ◽  
Transcriptional Program ◽  
Electrical Synapses ◽  
C Elegans

Electrical synapses are established between specific neurons and within distinct subcellular compartments, but the mechanisms that direct gap junction assembly in the nervous system are largely unknown. Here we show that a transcriptional program tunes cAMP signaling to direct the neuron-specific assembly and placement of electrical synapses in the C. elegans motor circuit. For these studies, we use live cell imaging to visualize electrical synapses in vivo and a novel optogenetic assay to confirm that they are functional. In VA motor neurons, the UNC-4 transcription factor blocks expression of cAMP antagonists that promote gap junction miswiring. In unc-4 mutants, VA electrical synapses are established with an alternative synaptic partner and are repositioned from the VA axon to soma. We show that cAMP counters these effects by driving gap junction trafficking into the VA axon for electrical synapse assembly. Thus, our experiments in an intact nervous system establish that cAMP regulates gap junction trafficking for the biogenesis of electrical synapses.

scholarly journals rab-27 acts in an intestinal secretory pathway to inhibit axon regeneration in C. elegans

2020 ◽  
Author(s):  
Alexander T. Lin-Moore ◽  
Motunrayo J. Oyeyemi ◽  
Marc Hammarlund
Keyword(s):  
Motor Neurons ◽  
Secretory Pathway ◽  
Axon Regeneration ◽  
Rab Gtpase ◽  
Long Distance ◽  
Extrinsic Factors ◽  
C Elegans ◽  
Cellular Environment ◽  
Neuropeptide Secretion ◽  
Neuronal Tissues

ABSTRACTInjured axons must regenerate to restore nervous system function, and regeneration is regulated in part by external factors from non-neuronal tissues. Many of these extrinsic factors act in the immediate cellular environment of the axon to promote or restrict regeneration, but the existence of long-distance signals regulating axon regeneration has not been clear. Here we show that the Rab GTPase rab-27 inhibits regeneration of GABAergic motor neurons in C. elegans through activity in the intestine. Re-expression of RAB-27, but not the closely related RAB-3, in the intestine of rab-27 mutant animals is sufficient to rescue normal regeneration. Several additional components of an intestinal neuropeptide secretion pathway also inhibit axon regeneration, including NPDC1/cab-1, SNAP25/aex-4, and KPC3/aex-5. Together these data indicate that RAB-27-dependent neuropeptide secretion from the intestine inhibits axon regeneration, and point to distal tissues as potent extrinsic regulators of regeneration.

scholarly journals Integrins Have Cell-Type-Specific Roles in the Development of Motor Neuron Connectivity

2019 ◽  
Vol 7 (3) ◽  
pp. 17 ◽  
Author(s):  
Devyn Oliver ◽  
Emily Norman ◽  
Heather Bates ◽  
Rachel Avard ◽  
Monika Rettler ◽  
...  
Keyword(s):  
Nervous System ◽  
Cell Adhesion ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Neuron Development ◽  
Wild Type ◽  
Cell Type ◽  
C Elegans ◽  
Cell Type Specific ◽  
Two Phases

Formation of the nervous system requires a complex series of events including proper extension and guidance of neuronal axons and dendrites. Here we investigate the requirement for integrins, a class of transmembrane cell adhesion receptors, in regulating these processes across classes of C. elegans motor neurons. We show α integrin/ina-1 is expressed by both GABAergic and cholinergic motor neurons. Despite this, our analysis of hypomorphic ina-1(gm144) mutants indicates preferential involvement of α integrin/ina-1 in GABAergic commissural development, without obvious involvement in cholinergic commissural development. The defects in GABAergic commissures of ina-1(gm144) mutants included both premature termination and guidance errors and were reversed by expression of wild type ina-1 under control of the native ina-1 promoter. Our results also show that α integrin/ina-1 is important for proper outgrowth and guidance of commissures from both embryonic and post-embryonic born GABAergic motor neurons, indicating an ongoing requirement for integrin through two phases of GABAergic neuron development. Our findings provide insights into neuron-specific roles for integrin that would not be predicted based solely upon expression analysis.

scholarly journals UBC-9 Acts in GABA Neurons to Control Neuromuscular Signaling in C. elegans

2020 ◽  
Vol 15 ◽  
pp. 263310552096279
Author(s):  
Victoria A Kreyden ◽  
Elly B Mawi ◽  
Kristen M Rush ◽  
Jennifer R Kowalski
Keyword(s):  
Nervous System ◽  
Synaptic Vesicle ◽  
Motor Neurons ◽  
Protein Function ◽  
Cholinergic Neurons ◽  
Synaptic Proteins ◽  
Inhibitory Synapses ◽  
C Elegans ◽  
Associated Proteins ◽  
Inhibitory Signaling

Regulation of excitatory to inhibitory signaling balance is essential to nervous system health and is maintained by numerous enzyme systems that modulate the activity, localization, and abundance of synaptic proteins. SUMOylation is a key post-translational regulator of protein function in diverse cells, including neurons. There, its role in regulating synaptic transmission through pre- and postsynaptic effects has been shown primarily at glutamatergic central nervous system synapses, where the sole SUMO-conjugating enzyme Ubc9 is a critical player. However, whether Ubc9 functions globally at other synapses, including inhibitory synapses, has not been explored. Here, we investigated the role of UBC-9 and the SUMOylation pathway in controlling the balance of excitatory cholinergic and inhibitory GABAergic signaling required for muscle contraction in Caenorhabditis elegans. We found inhibition or overexpression of UBC-9 in neurons modestly increased muscle excitation. Similar and even stronger phenotypes were seen with UBC-9 overexpression specifically in GABAergic neurons, but not in cholinergic neurons. These effects correlated with accumulation of synaptic vesicle-associated proteins at GABAergic presynapses, where UBC-9 and the C. elegans SUMO ortholog SMO-1 localized, and with defects in GABA-dependent behaviors. Experiments involving expression of catalytically inactive UBC-9 [UBC-9(C93S)], as well as co-expression of UBC-9 and SMO-1, suggested wild type UBC-9 overexpressed alone may act via substrate sequestration in the absence of sufficient free SUMO, underscoring the importance of tightly regulated SUMO enzyme function. Similar effects on muscle excitation, GABAergic signaling, and synaptic vesicle localization occurred with overexpression of the SUMO activating enzyme subunit AOS-1. Together, these data support a model in which UBC-9 and the SUMOylation system act at presynaptic sites in inhibitory motor neurons to control synaptic signaling balance in C. elegans. Future studies will be important to define UBC-9 targets at this synapse, as well as mechanisms by which UBC-9 and the SUMO pathway are regulated.

scholarly journals TheC. elegansephrin EFN-4 functions non-cell autonomously with heparan sulfate proteoglycans to promote axon outgrowth and branching

2015 ◽  
Author(s):  
Alicia A Schwieterman ◽  
Alyse N Steves ◽  
Vivian Yee ◽  
Cory J Donelson ◽  
Aaron Pital ◽  
...  
Keyword(s):  
Nervous System ◽  
Neurite Outgrowth ◽  
Motor Neurons ◽  
System Development ◽  
Nervous System Development ◽  
The Body ◽  
Tissue Type ◽  
Eph Receptors ◽  
C Elegans ◽  
Core Proteins

The Eph receptors and their cognate ephrin ligands play key roles in many aspects of nervous system development. These interactions typically occur within an individual tissue type, serving either to guide axons to their terminal targets or to define boundaries between the rhombomeres of the hindbrain. We have identified a novel role for theCaenorhabditis elegansephrin EFN-4 in promoting primary neurite outgrowth in AIY interneurons and D-class motor neurons. Rescue experiments reveal that EFN-4 functions non-cell autonomously in the epidermis to promote primary neurite outgrowth. We also find that EFN-4 plays a role in promoting ectopic axon branching in aC. elegansmodel of X-linked Kallmann syndrome. In this context, EFN-4 functions non-cell autonomously in the body wall muscle, and in parallel with HS biosynthesis genes and HSPG core proteins, which function cell autonomously in the AIY neurons. This is the first report of an epidermal ephrin providing a developmental cue to the nervous system.

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

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.

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

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.

The Circuit for Chemotaxis and Exploratory Behavior in Caenorhabditis Elegans

2017 ◽  
pp. 369-376
Author(s):  
Cornelia I. Bargmann
Keyword(s):  
Nervous System ◽  
Caenorhabditis Elegans ◽  
Sensory Neurons ◽  
Motor Neurons ◽  
Neuromuscular Junctions ◽  
Wiring Diagram ◽  
C Elegans ◽  
Section Electron ◽  
Adult Hermaphrodite ◽  
Electrophysiological Characterization

A wiring diagram of the Caenorhabditis elegans nervous system was constructed from serial-section electron micrographs 30 years ago. This wiring diagram divides the 302 neurons in the nervous system of the adult hermaphrodite into three overall classes: sensory neurons, motor neurons that form neuromuscular junctions, and interneurons that connect sensory neurons with motor neurons. Most sensory neurons and interneurons belong to bilaterally symmetric pairs with similar connections and morphologies, while motor neurons belong to larger classes. The C. elegans nervous system presents an exceptional situation in which neuroanatomical connections are extremely well defined and reproducible among animals. These detailed anatomical studies and a parallel genetic attack have increasingly been joined by functional and electrophysiological characterization.

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