scholarly journals Whole integration of neural connectomics, dynamics and bio-mechanics for identification of behavioral sensorimotor pathways in Caenorhabditis elegans

2019 ◽  
Author(s):  
Jimin Kim ◽  
Julia A. Santos ◽  
Mark J. Alkema ◽  
Eli Shlizerman
Keyword(s):  
Nervous System ◽  
Caenorhabditis Elegans ◽  
Large Scale ◽  
Neural Circuits ◽  
The Body ◽  
Neural Dynamics ◽  
Neural Pathways ◽  
Computational Approaches ◽  
External Forces

AbstractThe ability to fully discern how the brain orchestrates behavior requires the development of successful computational approaches to integrate and inform in-vivo investigations of the nervous system. To effectively assist with such investigations, computational approaches must be generic, scalable and unbiased. We propose such a comprehensive framework to investigate the interaction between the nervous system and the body for the nematode Caenorhabditis elegans (C. elegans). Specifically, we introduce a model that computationally emulates the activity of the complete somatic nervous system and its response to stimuli. The model builds upon the full anatomical wiring diagram, the connectome, and integrates it with additional layers including intra-cellular and extra-cellular bio-physically relevant neural dynamics, layers translating neural activity to muscle forces and muscle impulses to body postures. In addition, it implements inverse integration which modulates neural dynamics according to external forces on the body. We validate the model by in-silico injection of currents into sensory- and inter-neurons known to play a role in locomotion behaviors (e.g. posterior/anterior touch) and by applying external forces on the body. We are able to generate characteristic baseline locomotion behaviors (forward and backward movements). Inclusion of proprioceptive feedback, implemented through inverse integration, shows that feedback can entrain and sustain movements initiated by neural or mechanical triggers. We further apply neural stimuli, experimentally known to modulate locomotion, and show that our model supports natural behavioral responses such as turns, reversals and avoidance. The proposed model can be utilized to infer neural circuits involved in sensorimotor behavior. For this purpose, we develop large-scale computational ablation approaches such as (i) ablation survey and (ii) conditional ablation. Our results show how an ablation survey can identify neurons required for a ventral turning behavior. We also show how conditional ablation can identify alternative novel neural pathways, e.g. propose neurons which facilitate steering behavior towards olfactory attractants. The outcomes of our study show that the framework can be utilized to identify neural circuits, which control, mediate and generate natural behavior.

scholarly journals Food responsiveness regulates episodic behavioral states in Caenorhabditis elegans

2017 ◽  
Vol 117 (5) ◽  
pp. 1911-1934 ◽  
Author(s):  
Richard J. McCloskey ◽  
Anthony D. Fouad ◽  
Matthew A. Churgin ◽  
Christopher Fang-Yen
Keyword(s):  
Nervous System ◽  
Caenorhabditis Elegans ◽  
Body Movement ◽  
Egg Laying ◽  
The Body ◽  
Hierarchical Organization ◽  
Whole Body ◽  
Locomotory Activity ◽  
Behavioral States ◽  
External Environments

Animals optimize survival and reproduction in part through control of behavioral states, which depend on an organism’s internal and external environments. In the nematode Caenorhabditis elegans a variety of behavioral states have been described, including roaming, dwelling, quiescence, and episodic swimming. These states have been considered in isolation under varied experimental conditions, making it difficult to establish a unified picture of how they are regulated. Using long-term imaging, we examined C. elegans episodic behavioral states under varied mechanical and nutritional environments. We found that animals alternate between high-activity (active) and low-activity (sedentary) episodes in any mechanical environment, while the incidence of episodes and their behavioral composition depend on food levels. During active episodes, worms primarily roam, as characterized by continuous whole body movement. During sedentary episodes, animals exhibit dwelling (slower movements confined to the anterior half of the body) and quiescence (a complete lack of movement). Roaming, dwelling, and quiescent states are manifest not only through locomotory characteristics but also in pharyngeal pumping (feeding) and in egg-laying behaviors. Next, we analyzed the genetic basis of behavioral states. We found that modulation of behavioral states depends on neuropeptides and insulin-like signaling in the nervous system. Sensory neurons and the Foraging homolog EGL-4 regulate behavior through control of active/sedentary episodes. Optogenetic stimulation of dopaminergic and serotonergic neurons induced dwelling, implicating dopamine as a dwell-promoting neurotransmitter. Our findings provide a more unified description of behavioral states and suggest that perception of nutrition is a conserved mechanism for regulating animal behavior. NEW & NOTEWORTHY One strategy by which animals adapt to their internal states and external environments is by adopting behavioral states. The roundworm Caenorhabditis elegans is an attractive model for investigating how behavioral states are genetically and neuronally controlled. Here we describe the hierarchical organization of behavioral states characterized by locomotory activity, feeding, and egg-laying. We show that decisions to engage in these behaviors are controlled by the nervous system through insulin-like signaling and the perception of food.

scholarly journals Large-Scale Chronically Implantable Precision Motorized Microdrive Array for Freely Behaving Animals

2008 ◽  
Vol 100 (4) ◽  
pp. 2430-2440 ◽  
Author(s):  
Jun Yamamoto ◽  
Matthew A. Wilson
Keyword(s):  
Single Unit ◽  
Large Scale ◽  
Neural Circuits ◽  
Brain Regions ◽  
Unit Recording ◽  
Chronic Recording ◽  
Large Numbers ◽  
Freely Behaving

Multiple single-unit recording has become one of the most powerful in vivo electro-physiological techniques for studying neural circuits. The demand has been increasing for small and lightweight chronic recording devices that allow fine adjustments to be made over large numbers of electrodes across multiple brain regions. To achieve this, we developed precision motorized microdrive arrays that use a novel motor multiplexing headstage to dramatically reduce wiring while preserving precision of the microdrive control. Versions of the microdrive array were chronically implanted on both rats (21 microdrives) and mice (7 microdrives), and relatively long-term recordings were taken.

scholarly journals Large scale in vivo recording of sensory neuron activity with GCaMP6

2017 ◽  
Author(s):  
Kim I Chisholm ◽  
Nikita Khovanov ◽  
Douglas M Lopes ◽  
Federica La Russa ◽  
Stephen B McMahon
Keyword(s):  
Nervous System ◽  
Peripheral Nervous System ◽  
Sensory Neurons ◽  
Action Potentials ◽  
Large Scale ◽  
Primary Afferents ◽  
Neuron Activity ◽  
Functional Responses ◽  
Single Action

AbstractGreater emphasis on the study of intact cellular networks in their physiological environment has led to rapid advances in intravital imaging in the central nervous system, while the peripheral system remains largely unexplored. To assess large networks of sensory neurons we selectively label primary afferents with GCaMP6s and visualise their functional responses in vivo to peripheral stimulation. We show that we are able to monitor simultaneously the activity of hundreds of sensory neurons with sensitivity sufficient to detect, in most cases, single action potentials with a typical rise time of around 200 milliseconds, and an exponential decay with a time constant of approximately 700 milliseconds. Using this sensitive technique we are able to show that large scale recordings demonstrate the recently disputed polymodality of nociceptive primary afferents with between 40-80% of thermally sensitive DRG neurons responding also to noxious mechanical stimulation. We also specifically assess the small population of peripheral cold fibres and demonstrate significant sensitisation to cooling after a model of sterile and persistent inflammation, with significantly increased sensitivity already at decreases of 5°C when compared to uninflamed responses. This not only reveals interesting new insights into the (patho)physiology of the peripheral nervous system but also demonstrates the sensitivity of this imaging technique to physiological changes in primary afferents.Significance StatementMost of our functional understanding of the peripheral nervous system has come from single unit recordings. However, the acquisition of such data is labour-intensive and usually ‘low yield’. Moreover, some questions are best addressed by studying populations of neurons. To this end we report on a system that monitors activity in hundreds of single sensory neurons simultaneously, with sufficient sensitivity to detect in most cases single action potentials. We use this technique to characterise nociceptor properties and demonstrate polymodality in the majority of neurons and their sensitization under inflammatory conditions. We therefore believe this approach will be very useful for the studies of the somatosensory system in general and pain in particular.

scholarly journals Correlated Light-Serial Scanning Electron Microscopy (CoLSSEM) for ultrastructural visualization of single neurons in vivo

2017 ◽  
Author(s):  
Yusuke Hirabayashi ◽  
Juan Carlos Tapia ◽  
Franck Polleux
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Large Scale ◽  
Neural Circuits ◽  
Structural Connectivity ◽  
Synaptic Connections ◽  
General Applicability ◽  
Fluorescent Reporter ◽  
Scanning Electron

A challenging aspect of neuroscience revolves around mapping the synaptic connections within neural circuits (connectomics) over scales spanning several orders of magnitude (nanometers to meters). Despite significant improvements in serial section electron microscopy (SSEM) technologies, several major roadblocks have impaired its general applicability to mammalian neural circuits. In the present study, we introduce a new approach that circumvents these roadblocks by adapting a genetically-encoded ascorbate peroxidase (APEX2) as a fusion protein to a membrane-targeted fluorescent reporter (CAAX-Venus), and introduce it in single pyramidal neurons in vivo using extremely sparse in utero cortical electroporation (IUCE). This approach allows to perform Correlated Light-SSEM (CoLSSEM) on individual neurons, reconstructing their dendritic and axonal arborization in a targeted way via combination of high-resolution confocal microscopy, and subsequently imaging of its ultrastuctural features and synaptic connections with the ATUM-SEM (automated tape-collecting ultramicrotome - scanning electron microscopy) technology. Our method significantly improves the the feasibility of large-scale reconstructions of neurons within a circuit, and bridges the description of ultrastructural features of genetically-identified neurons with their functional and/or structural connectivity, one of the main goal of connectomics.

scholarly journals Caenorhabditis elegans, a Host to Investigate the Probiotic Properties of Beneficial Microorganisms

2020 ◽  
Vol 7 ◽  
Author(s):  
Cyril Poupet ◽  
Christophe Chassard ◽  
Adrien Nivoliez ◽  
Stéphanie Bornes
Keyword(s):  
Caenorhabditis Elegans ◽  
High Throughput Screening ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Probiotic Properties ◽  
C Elegans ◽  
Probiotic Potential ◽  
Challenges And Opportunities ◽  
Future Challenges

Caenorhabditis elegans, a non-parasitic nematode emerges as a relevant and powerful candidate as an in vivo model for microorganisms-microorganisms and microorganisms-host interactions studies. Experiments have demonstrated the probiotic potential of bacteria since they can provide to the worm a longer lifespan, an increased resistance to pathogens and to oxidative or heat stresses. Probiotics are used to prevent or treat microbiota dysbiosis and associated pathologies but the molecular mechanisms underlying their capacities are still unknown. Beyond safety and healthy aspects of probiotics, C. elegans represents a powerful way to design large-scale studies to explore transkingdom interactions and to solve questioning about the molecular aspect of these interactions. Future challenges and opportunities would be to validate C. elegans as an in vivo tool for high-throughput screening of microorganisms for their potential probiotic use on human health and to enlarge the panels of microorganisms studied as well as the human diseases investigated.

scholarly journals Chlorophyll enhances oxidative stress tolerance inCaenorhabditis elegansand extends its lifespan

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1879 ◽  
Author(s):  
Erjia Wang ◽  
Michael Wink
Keyword(s):  
Oxidative Stress ◽  
Caenorhabditis Elegans ◽  
Secondary Metabolites ◽  
Model System ◽  
The Body ◽  
Aging Effects ◽  
Oxidative Stress Tolerance ◽  
C Elegans ◽  
Dependent Pathway

Green vegetables are thought to be responsible for several beneficial properties such as antioxidant, anti-mutagenic, and detoxification activities. It is not known whether these effects are due to chlorophyll which exists in large amounts in many foods or result from other secondary metabolites. In this study, we used the model systemCaenorhabditis elegansto investigate the anti-oxidative and anti-aging effects of chlorophyllin vivo. We found that chlorophyll significantly improves resistance to oxidative stress. It also enhances the lifespan ofC. elegansby up to 25% via activation of the DAF-16/FOXO-dependent pathway. The results indicate that chlorophyll is absorbed by the worms and is thus bioavailable, constituting an important prerequisite for antioxidant and longevity-promoting activities inside the body. Our study thereby supports the view that green vegetables may also be beneficial for humans.

scholarly journals The Reissner Fiber is Highly Dynamic in vivo and Controls Morphogenesis of the Spine

2019 ◽  
Author(s):  
Benjamin Troutwine ◽  
Paul Gontarz ◽  
Ryoko Minowa ◽  
Adrian Monstad-Rios ◽  
Mia J. Konjikusic ◽  
...  
Keyword(s):  
Nervous System ◽  
Embryonic Development ◽  
Dynamic Properties ◽  
Central Canal ◽  
The Body ◽  
Body Axis ◽  
List Type ◽  
The Central Nervous System ◽  
Spine Morphogenesis

SummarySpine morphogenesis requires the integration of multiple musculoskeletal tissues with the nervous system. Cerebrospinal fluid (CSF) physiology is important for development and homeostasis of the central nervous system and its disruption has been linked to scoliosis in zebrafish [1, 2]. Suspended in the CSF is an enigmatic glycoprotein thread called the Reissner fiber, which is secreted from the subcomissural organ (SCO) in the brain and extends caudally through the central canal to where it terminates at the base of the spinal cord. In zebrafish, scospondin null mutants are unable to assemble the Reissner fiber and fail to extend a straight body axis during embryonic development [3]. Here, we describe zebrafish hypomorphic missense alleles, which assemble the Reissner fiber and straighten the body axis during early embryonic development, yet progressively lose the fiber, concomitant with the emergence of body curvature, alterations in neuronal gene expression, and scoliosis in adults. Using an endogenously tagged scospondin-GFP zebrafish knock-in line, we directly visualized Reissner fiber dynamics during the normal development and during the progression of scoliosis, and demonstrate that the Reissner fiber is critical for the morphogenesis of the spine. Our study establishes a framework for future investigations of mechanistic roles of the Reissner fiber including its dynamic properties, molecular interactions, and how these processes are involved in the regulation of spine morphogenesis and scoliosis.HighlightsHypomorphic mutations in zebrafish scospondin result in progressive scoliosisThe disassembly of the Reissner fiber in scospondin hypomorphic mutants results in the strong upregulation of neuronal receptors and synaptic transport componentsAn endogenous fluorescent knock-in allele of scospondin reveals dynamic properties of the Reissner fiber during zebrafish developmentLoss of the Reissner fiber during larval development is a common feature of zebrafish scoliosis models

Growth cones stall and collapse during axon outgrowth in Caenorhabditis elegans

Development ◽  
1999 ◽  
Vol 126 (20) ◽  
pp. 4489-4498 ◽  
Author(s):  
K.M. Knobel ◽  
E.M. Jorgensen ◽  
M.J. Bastiani
Keyword(s):  
Caenorhabditis Elegans ◽  
Growth Cone ◽  
Nerve Cord ◽  
Body Wall ◽  
Growth Cones ◽  
The Body ◽  
Axon Outgrowth ◽  
Attachment Structures ◽  
Dorsal Nerve

During nervous system development, neurons form synaptic contacts with distant target cells. These connections are formed by the extension of axonal processes along predetermined pathways. Axon outgrowth is directed by growth cones located at the tips of these neuronal processes. Although the behavior of growth cones has been well-characterized in vitro, it is difficult to observe growth cones in vivo. We have observed motor neuron growth cones migrating in living Caenorhabditis elegans larvae using time-lapse confocal microscopy. Specifically, we observed the VD motor neurons extend axons from the ventral to dorsal nerve cord during the L2 stage. The growth cones of these neurons are round and migrate rapidly across the epidermis if they are unobstructed. When they contact axons of the lateral nerve fascicles, growth cones stall and spread out along the fascicle to form anvil-shaped structures. After pausing for a few minutes, they extend lamellipodia beyond the fascicle and resume migration toward the dorsal nerve cord. Growth cones stall again when they contact the body wall muscles. These muscles are tightly attached to the epidermis by narrowly spaced circumferential attachment structures. Stalled growth cones extend fingers dorsally between these hypodermal attachment structures. When a single finger has projected through the body wall muscle quadrant, the growth cone located on the ventral side of the muscle collapses and a new growth cone forms at the dorsal tip of the predominating finger. Thus, we observe that complete growth cone collapse occurs in vivo and not just in culture assays. In contrast to studies indicating that collapse occurs upon contact with repulsive substrata, collapse of the VD growth cones may result from an intrinsic signal that serves to maintain growth cone primacy and conserve cellular material.

scholarly journals Neural reflexes in inflammation and immunity

2012 ◽  
Vol 209 (6) ◽  
pp. 1057-1068 ◽  
Author(s):  
Ulf Andersson ◽  
Kevin J. Tracey
Keyword(s):  
Nervous System ◽  
Neural Circuits ◽  
Therapeutic Benefit ◽  
Systems Development ◽  
Neural Pathways ◽  
Organ Function ◽  
Pharmacological Agents ◽  
Immunological Homeostasis ◽  
Mammalian Immune System ◽  
Systems Failure

The mammalian immune system and the nervous system coevolved under the influence of infection and sterile injury. Knowledge of homeostatic mechanisms by which the nervous system controls organ function was originally applied to the cardiovascular, gastrointestinal, musculoskeletal, and other body systems. Development of advanced neurophysiological and immunological techniques recently enabled the study of reflex neural circuits that maintain immunological homeostasis, and are essential for health in mammals. Such reflexes are evolutionarily ancient, dating back to invertebrate nematode worms that possess primitive immune and nervous systems. Failure of these reflex mechanisms in mammals contributes to nonresolving inflammation and disease. It is also possible to target these neural pathways using electrical nerve stimulators and pharmacological agents to hasten the resolution of inflammation and provide therapeutic benefit.

scholarly journals Elevated CO2 regulates the Wnt signaling pathway in mammals, Drosophila melanogaster and Caenorhabditis elegans

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Masahiko Shigemura ◽  
Emilia Lecuona ◽  
Martín Angulo ◽  
Laura A. Dada ◽  
Melanie B. Edwards ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Caenorhabditis Elegans ◽  
Wnt Signaling ◽  
Large Scale ◽  
Wnt Pathway ◽  
Wnt Signaling Pathway ◽  
Secondary Analysis ◽  
Evolutionarily Conserved ◽  
Integrated Or

AbstractCarbon dioxide (CO2) is sensed by cells and can trigger signals to modify gene expression in different tissues leading to changes in organismal functions. Despite accumulating evidence that several pathways in various organisms are responsive to CO2 elevation (hypercapnia), it has yet to be elucidated how hypercapnia activates genes and signaling pathways, or whether they interact, are integrated, or are conserved across species. Here, we performed a large-scale transcriptomic study to explore the interaction/integration/conservation of hypercapnia-induced genomic responses in mammals (mice and humans) as well as invertebrates (Caenorhabditis elegans and Drosophila melanogaster). We found that hypercapnia activated genes that regulate Wnt signaling in mouse lungs and skeletal muscles in vivo and in several cell lines of different tissue origin. Hypercapnia-responsive Wnt pathway homologues were similarly observed in secondary analysis of available transcriptomic datasets of hypercapnia in a human bronchial cell line, flies and nematodes. Our data suggest the evolutionarily conserved role of high CO2 in regulating Wnt pathway genes.

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