scholarly journals Volumetric reconstruction of main Caenorhabditis elegans neuropil at two different time points

2018 ◽  
Author(s):  
Christopher A Brittin ◽  
Steven J Cook ◽  
David H Hall ◽  
Scott W Emmons ◽  
Netta Cohen
Keyword(s):  
Spatial Information ◽  
Genetic Model ◽  
Nerve Ring ◽  
Synaptic Connectivity ◽  
Spatial Proximity ◽  
Detailed Knowledge ◽  
Synaptic Specificity ◽  
Time Points ◽  
C Elegans ◽  
Volumetric Reconstruction

Detailed knowledge of both synaptic connectivity and the spatial proximity of neurons is crucial for understanding wiring specificity in the nervous system. Here, we volumetrically reconstructed the C. Elegans nerve ring from legacy serial-sectioned electron micrographs at two distinct time points: the L4 and young adult. The new volumetric reconstructions provide detailed spatial and morphological information of neural processes in the nerve ring. Our analysis suggests that the nerve ring exhibits three levels of wiring specificity: spatial, synaptic and subcellular. Neuron classes innervate well defined neighborhoods and aggregate functionally similar synapses to support distinct computational pathways. Connectivity fractions vary based on neuron class and synapse type. We find that the variability in process placement accounts for less than 20% of the variability in synaptic connectivity and models based only on spatial information cannot account for the reproducibility of synaptic connections among homologous neurons. This suggests that additional, non-spatial factors also contribute to synaptic and subcellular specificity. With this in mind, we conjecture that a spatially constrained, genetic model could provide sufficient synaptic specificity. Using a model of cell-specific combinatorial genetic expression, we show that additional specificity, such as sub-cellular domains or alternative splicing, would be required to reproduce the wiring specificity in the nerve ring.

scholarly journals A neurite-zippering mechanism, mediated by layer-specific expression of IgCAMs, regulates synaptic laminar specificity in the C. elegans nerve ring neuropil

2020 ◽  
Author(s):  
Titas Sengupta ◽  
Noelle L. Koonce ◽  
Mark W. Moyle ◽  
Leighton H. Duncan ◽  
Nabor Vázquez-Martínez ◽  
...  
Keyword(s):  
Adhesion Molecules ◽  
Design Principle ◽  
Brain Structures ◽  
Nerve Ring ◽  
Learning Approaches ◽  
Specific Expression ◽  
Synaptic Specificity ◽  
C Elegans ◽  
Regulated Expression ◽  
Laminar Specificity

AbstractA fundamental design principle of nervous systems is the grouping of neuronal contacts into layers within nerve bundles. The layered arrangement of neurites requires nanoscale precision in their placement within bundles, and this precision, which can not be exclusively explained by simple tip-directed outgrowth dynamics, underpins synaptic specificity and circuit architecture. Here we implement novel imaging methods and deep learning approaches to document the specific placement of single neurites during the assembly of the C. elegans nerve ring. We uncover a zippering mechanism that controls precise placement of neurites onto specific layer subdomains. Nanoscale precision in neurite placement is orchestrated via temporally-regulated expression of specific Ig adhesion molecules, such as SYG-1. Ig adhesion molecules act as instructive signals, defining sublaminar regions and guiding neurite zippering onto target neurons. Our study reveals novel developmental mechanisms that coordinate neurite placement and synaptic specificity within layered brain structures.

scholarly journals Beyond the connectome: A map of a brain architecture derived from whole-brain volumetric reconstructions

2020 ◽  
Author(s):  
Christopher A. Brittin ◽  
Steven J. Cook ◽  
David H. Hall ◽  
Scott W. Emmons ◽  
Netta Cohen
Keyword(s):  
Nervous System ◽  
System Organization ◽  
Nerve Ring ◽  
Behavioral Impairment ◽  
Brain Organization ◽  
C Elegans ◽  
Volumetric Reconstruction ◽  
High Level ◽  
Gap Junctional ◽  
The Brain

ABSTRACTAnimal nervous system organization is crucial for all body functions and its disruption can manifest in severe cognitive and behavioral impairment. This organization relies on features across scales, from nano-level localization of synapses, through multiplicities of neuronal morphologies and their contribution to circuit organization, to the high level stereotyped connections between different regions of the brain. The sheer complexity of this organ means that to date, we have yet to reconstruct and model the structure of a complete nervous system that is integrated across all these scales. Here, we present a complete structure-function model of the nematode C. elegans main neuropil, the nerve ring, which we derive by integrating the volumetric reconstruction from two animals with corresponding synaptic and gap junctional connectomes. Whereas previously the nerve ring was considered a densely packed tract of axons, we uncover internal organization into 5 functional bundles and show how they spatially constrain and support the synaptic connectome. We find that the C. elegans connectome is not invariant, but that a precisely wired core circuit is embedded in a background of variable connectivity, and propose a corresponding reference connectome for the core circuit. Using this reference, we show that the architecture of the C. elegans brain can be viewed as a modular Residual Network that supports sensory computation and integration, sensory-motor convergence, and brain-wide coordination. These findings point to scalable and robust features of brain organization that are likely universal across phyla.

scholarly journals Caenorhabditis elegans as an in vivo Model to Assess Amphetamine Tolerance

2021 ◽  
pp. 1-9
Author(s):  
Dayana Torres Valladares ◽  
Sirisha Kudumala ◽  
Murad Hossain ◽  
Lucia Carvelli
Keyword(s):  
Caenorhabditis Elegans ◽  
Molecular Mechanisms ◽  
Drugs Of Abuse ◽  
Genetic Model ◽  
In Vivo Model ◽  
C Elegans ◽  
Hyperactivity Disorder ◽  
In Vitro Data

Amphetamine is a potent psychostimulant also used to treat attention deficit/hyperactivity disorder and narcolepsy. In vivo and in vitro data have demonstrated that amphetamine increases the amount of extra synaptic dopamine by both inhibiting reuptake and promoting efflux of dopamine through the dopamine transporter. Previous studies have shown that chronic use of amphetamine causes tolerance to the drug. Thus, since the molecular mechanisms underlying tolerance to amphetamine are still unknown, an animal model to identify the neurochemical mechanisms associated with drug tolerance is greatly needed. Here we took advantage of a unique behavior caused by amphetamine in <i>Caenorhabditis elegans</i> to investigate whether this simple, but powerful, genetic model develops tolerance following repeated exposure to amphetamine. We found that at least 3 treatments with 0.5 mM amphetamine were necessary to see a reduction in the amphetamine-induced behavior and, thus, to promote tolerance. Moreover, we found that, after intervals of 60/90 minutes between treatments, animals were more likely to exhibit tolerance than animals that underwent 10-minute intervals between treatments. Taken together, our results show that <i>C. elegans</i> is a suitable system to study tolerance to drugs of abuse such as amphetamines.

Neuropeptide signalling shapes feeding and reproductive behaviours in male C. elegans

2021 ◽  
Author(s):  
Matthew J Gadenne ◽  
Iris Hardege ◽  
Djordji Suleski ◽  
Paris Jaggers ◽  
Isabel Beets ◽  
...  
Keyword(s):  
Synaptic Connectivity ◽  
Male Mating ◽  
Sexually Dimorphic ◽  
C Elegans ◽  
Mating Efficiency ◽  
Sexually Dimorphic Expression ◽  
Pharyngeal Pumping ◽  
Insight Into ◽  
Feeding Behaviours ◽  
Dimorphic Expression

Sexual dimorphism occurs where different sexes of the same species display differences in characteristics not limited to reproduction. For the nematode Caenorhabditis elegans, in which the complete neuroanatomy has been solved for both hermaphrodites and males, sexually dimorphic features have been observed both in terms of the number of neurons and in synaptic connectivity. In addition, male behaviours, such as food-leaving to prioritise searching for mates, have been attributed to neuropeptides released from sex-shared or sex-specific neurons. In this study, we show that the lury-1 neuropeptide gene shows a sexually dimorphic expression pattern; being expressed in pharyngeal neurons in both sexes but displaying additional expression in tail neurons only in the male. We also show that lury-1 mutant animals show sex differences in feeding behaviours, with pharyngeal pumping elevated in hermaphrodites but reduced in males. LURY-1 also modulates male mating efficiency, influencing motor events during contact with a hermaphrodite. Our findings indicate sex-specific roles of this peptide in feeding and reproduction in C. elegans, providing further insight into neuromodulatory control of sexually dimorphic behaviours.

scholarly journals MINING CO-LOCATION PATTERNS FROM SPATIAL DATA

2016 ◽  
Vol III-2 ◽  
pp. 85-90
Author(s):  
C. Zhou ◽  
W. D. Xiao ◽  
D. Q. Tang
Keyword(s):  
Spatial Data ◽  
Spatial Information ◽  
Spatial Proximity ◽  
Widespread Application ◽  
Location Pattern ◽  
Gps Technology ◽  
Location Patterns ◽  
Mining Algorithms ◽  
The City ◽  
Research Domains

Due to the widespread application of geographic information systems (GIS) and GPS technology and the increasingly mature infrastructure for data collection, sharing, and integration, more and more research domains have gained access to high-quality geographic data and created new ways to incorporate spatial information and analysis in various studies. There is an urgent need for effective and efficient methods to extract unknown and unexpected information, e.g., co-location patterns, from spatial datasets of high dimensionality and complexity. A co-location pattern is defined as a subset of spatial items whose instances are often located together in spatial proximity. Current co-location mining algorithms are unable to quantify the spatial proximity of a co-location pattern. We propose a co-location pattern miner aiming to discover co-location patterns in a multidimensional spatial data by measuring the cohesion of a pattern. We present a model to measure the cohesion in an attempt to improve the efficiency of existing methods. The usefulness of our method is demonstrated by applying them on the publicly available spatial data of the city of Antwerp in Belgium. The experimental results show that our method is more efficient than existing methods.

scholarly journals Alzheimer’s disease-relevant tau modifications selectively impact neurodegeneration and mitophagy in a novel C. elegans single-copy transgenic model

2020 ◽  
Author(s):  
Sanjib Guha ◽  
Sarah Fischer ◽  
Gail VW Johnson ◽  
Keith Nehrke
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genetic Model ◽  
Neurodegenerative Disorder ◽  
Model Organism ◽  
Single Copy ◽  
Mitochondrial Stress ◽  
C Elegans ◽  
Touch Receptor Neurons ◽  
New Perspective

ABSTRACTBackgroundA defining pathological hallmark of the progressive neurodegenerative disorder Alzheimer’s disease (AD) is the accumulation of misfolded tau with abnormal post-translational modifications (PTMs). These include phosphorylation at Threonine 231 (T231) and acetylation at Lysine 274 (K274) and at Lysine 281 (K281). Although tau is recognized to play a central role in pathogenesis of AD, the precise mechanisms by which these abnormal PTMs contribute to the neural toxicity of tau is unclear.MethodsHuman 0N4R tau (wild type) was expressed in touch receptor neurons of the genetic model organism C. elegans through single-copy gene insertion. Defined mutations were then introduced into the single-copy tau transgene through CRISPR-Cas9 genome editing. These mutations included T231E and T231A, to mimic phosphorylation and phospho-ablation of a commonly observed pathological epitope, respectively, and K274/281Q, to mimic disease-associated lysine acetylation. Stereotypical touch response assays were used to assess behavioral defects in the transgenic strains as a function of age, and genetically-encoded fluorescent biosensors were used to measure the morphological dynamics and turnover of touch neuron mitochondria.ResultsUnlike existing tau overexpression models, C. elegans single-copy expression of tau did not elicit overt pathological phenotypes at baseline. However, strains expressing disease associated PTM-mimetics (T231E and K274/281Q) exhibited reduced touch sensation and morphological abnormalities that increased with age. In addition, the PTM-mimetic mutants lacked the ability to engage mitophagy in response to mitochondrial stress.ConclusionsLimiting the expression of tau results in a genetic model where pathological modifications and age result in evolving phenotypes, which may more closely resemble the normal progression of AD. The finding that disease-associated PTMs suppress compensatory responses to mitochondrial stress provides a new perspective into the pathogenic mechanisms underlying AD.

scholarly journals Molecular basis of synaptic specificity by immunoglobulin superfamily receptors in Drosophila

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Shouqiang Cheng ◽  
James Ashley ◽  
Justyna D Kurleto ◽  
Meike Lobb-Rabe ◽  
Yeonhee Jenny Park ◽  
...  
Keyword(s):  
Axon Guidance ◽  
Molecular Basis ◽  
Surface Proteins ◽  
Synaptic Connectivity ◽  
Immunoglobulin Superfamily ◽  
Neuronal Connectivity ◽  
Cell Surface Proteins ◽  
Synaptic Specificity ◽  
Immunoglobulin Superfamily Proteins ◽  
Synapse Targeting

In stereotyped neuronal networks, synaptic connectivity is dictated by cell surface proteins, which assign unique identities to neurons, and physically mediate axon guidance and synapse targeting. We recently identified two groups of immunoglobulin superfamily proteins in Drosophila, Dprs and DIPs, as strong candidates for synapse targeting functions. Here, we uncover the molecular basis of specificity in Dpr–DIP mediated cellular adhesions and neuronal connectivity. First, we present five crystal structures of Dpr–DIP and DIP–DIP complexes, highlighting the evolutionary and structural origins of diversification in Dpr and DIP proteins and their interactions. We further show that structures can be used to rationally engineer receptors with novel specificities or modified affinities, which can be used to study specific circuits that require Dpr–DIP interactions to help establish connectivity. We investigate one pair, engineered Dpr10 and DIP-α, for function in the neuromuscular circuit in flies, and reveal roles for homophilic and heterophilic binding in wiring.

scholarly journals Multicellular rosettes organize neuropil formation

2020 ◽  
Author(s):  
Christopher A. Brittin ◽  
Anthony Santella ◽  
Kristopher Barnes ◽  
Mark W. Moyle ◽  
Li Fan ◽  
...  
Keyword(s):  
Functional Organization ◽  
Critical Role ◽  
Ring Structure ◽  
Nerve Ring ◽  
Cell Behaviors ◽  
Dense Networks ◽  
C Elegans ◽  
Single Axon ◽  
Organizational Features

SummaryNeuropils are compartments in the nervous system containing dense networks of neurites and synapses which function as information processing centers. Neuropil formation requires structural and functional organization at and across different scales, achieving single-axon precision for circuits that carry out the core functions while simultaneously accommodating variability among individuals [1; 2; 3; 4]. How these organizational features emerge over development is poorly understood. The nerve ring is the primary neuropil in C. elegans, and its structure is thoroughly mapped [5; 6]. We show that prior to axon outgrowth, nerve ring neurons form a ring of multicellular rosettes with surrounding cells to organize the stratified nerve ring structure [7; 8]. Axon bundles which correspond to future nerve ring strata grow from rosette centers, travel along the ring on “bridge” cells that are simultaneously engaged in adjacent rosettes, and assemble into a topographic scaffold of the nerve ring. SAX-3/Robo is required for proper rosette formation and outgrowth from the center. Furthermore, axon contact sites that form early in development are more conserved than the later ones, indicating a temporal component in neuropil structural variability. Our results reveal an unexpected and critical role of collective cell behaviors prior to innervation to pattern a complex neuropil and orchestrate its formation across scales.

User-Centric Similarity and Proximity Measures for Spatial Personalization

2010 ◽  
Vol 6 (2) ◽  
pp. 59-78 ◽  
Author(s):  
Yanwu Yang ◽  
Christophe Claramunt ◽  
Marie-Aude Aufaure ◽  
Wensheng Zhang
Keyword(s):  
Information Needs ◽  
Spatial Information ◽  
Personal Information ◽  
Similarity Measures ◽  
Spatial Proximity ◽  
Mobile Environments ◽  
Conceptual Approach ◽  
Semantic Domain ◽  
User Centric ◽  
Proximity Measures

Spatial personalization can be defined as a novel way to fulfill user information needs when accessing spatial information services either on the web or in mobile environments. The research presented in this paper introduces a conceptual approach that models the spatial information offered to a given user into a user-centered conceptual map, and spatial proximity and similarity measures that considers her/his location, interests and preferences. This approach is based on the concepts of similarity in the semantic domain, and proximity in the spatial domain, but taking into account user’s personal information. Accordingly, these spatial proximity and similarity measures could directly support derivation of personalization services and refinement of the way spatial information is accessible to the user in spatially related applications. These modeling approaches are illustrated by some experimental case studies.

scholarly journals Computational inference of the molecular logic for synaptic connectivity in C. elegans

2006 ◽  
Vol 22 (14) ◽  
pp. e497-e506 ◽  
Author(s):  
V. Varadan ◽  
D. M. Miller ◽  
D. Anastassiou
Keyword(s):  
Synaptic Connectivity ◽  
C Elegans ◽  
Molecular Logic ◽  
Computational Inference
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