scholarly journals Neurexin directs partner-specific synaptic connectivity in C. elegans

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Alison Philbrook ◽  
Shankar Ramachandran ◽  
Christopher M Lambert ◽  
Devyn Oliver ◽  
Jeremy Florman ◽  
...  
Keyword(s):  
Neuromuscular Transmission ◽  
Molecular Mechanisms ◽  
Neural Circuits ◽  
Cholinergic Receptor ◽  
Gabaergic Neurons ◽  
Synaptic Connectivity ◽  
Receptor Clustering ◽  
Molecular Control ◽  
C Elegans ◽  
Excitatory Transmission

In neural circuits, individual neurons often make projections onto multiple postsynaptic partners. Here, we investigate molecular mechanisms by which these divergent connections are generated, using dyadic synapses in C. elegans as a model. We report that C. elegans nrx-1/neurexin directs divergent connectivity through differential actions at synapses with partnering neurons and muscles. We show that cholinergic outputs onto neurons are, unexpectedly, located at previously undefined spine-like protrusions from GABAergic dendrites. Both these spine-like features and cholinergic receptor clustering are strikingly disrupted in the absence of nrx-1. Excitatory transmission onto GABAergic neurons, but not neuromuscular transmission, is also disrupted. Our data indicate that NRX-1 located at presynaptic sites specifically directs postsynaptic development in GABAergic neurons. Our findings provide evidence that individual neurons can direct differential patterns of connectivity with their post-synaptic partners through partner-specific utilization of synaptic organizers, offering a novel view into molecular control of divergent connectivity.

scholarly journals A multicellular rosette-mediated collective dendrite extension

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Li Fan ◽  
Ismar Kovacevic ◽  
Maxwell G Heiman ◽  
Zhirong Bao
Keyword(s):  
Adhesion Molecules ◽  
Molecular Mechanisms ◽  
Neural Circuits ◽  
Sensory Nerve ◽  
Neuronal Cell ◽  
Sensory Organ ◽  
Neurite Extension ◽  
C Elegans ◽  
Neuronal Cell Bodies

Coordination of neurite morphogenesis with surrounding tissues is crucial to the establishment of neural circuits, but the underlying cellular and molecular mechanisms remain poorly understood. We show that neurons in a C. elegans sensory organ, called the amphid, undergo a collective dendrite extension to form the sensory nerve. The amphid neurons first assemble into a multicellular rosette. The vertex of the rosette, which becomes the dendrite tips, is attached to the anteriorly migrating epidermis and carried to the sensory depression, extruding the dendrites away from the neuronal cell bodies. Multiple adhesion molecules including DYF-7, SAX-7, HMR-1 and DLG-1 function redundantly in rosette-to-epidermis attachment. PAR-6 is localized to the rosette vertex and dendrite tips, and promotes DYF-7 localization and dendrite extension. Our results suggest a collective mechanism of neurite extension that is distinct from the classical pioneer-follower model and highlight the role of mechanical cues from surrounding tissues in shaping neurites.

Neural Circuits of Sexual Behavior inCaenorhabditis elegans

2018 ◽  
Vol 41 (1) ◽  
pp. 349-369 ◽  
Author(s):  
Scott W. Emmons
Keyword(s):  
Nervous System ◽  
Sex Differences ◽  
Sexual Behaviors ◽  
Neural Circuits ◽  
Egg Laying ◽  
Synaptic Connectivity ◽  
Comprehensive Description ◽  
C Elegans ◽  
Shared Component ◽  
Male Specific

The recently determined connectome of the Caenorhabditis elegans adult male, together with the known connectome of the hermaphrodite, opens up the possibility for a comprehensive description of sexual dimorphism in this species and the identification and study of the neural circuits underlying sexual behaviors. The C. elegans nervous system consists of 294 neurons shared by both sexes plus neurons unique to each sex, 8 in the hermaphrodite and 91 in the male. The sex-specific neurons are well integrated within the remainder of the nervous system; in the male, 16% of the input to the shared component comes from male-specific neurons. Although sex-specific neurons are involved primarily, but not exclusively, in controlling sex-unique behavior—egg-laying in the hermaphrodite and copulation in the male—these neurons act together with shared neurons to make navigational choices that optimize reproductive success. Sex differences in general behaviors are underlain by considerable dimorphism within the shared component of the nervous system itself, including dimorphism in synaptic connectivity.

scholarly journals Neuron tracing and quantitative analyses of dendritic architecture reveal symmetrical three-way-junctions and phenotypes of git-1 in C. elegans

2021 ◽  
Author(s):  
Omer Yuval ◽  
Yael Iosilevskii ◽  
Benjamin Podbilewicz ◽  
Tom Shemesh
Keyword(s):  
Molecular Mechanisms ◽  
Dendritic Tree ◽  
Structural Features ◽  
Dendritic Morphology ◽  
Control Mechanisms ◽  
Molecular Control ◽  
Dendritic Trees ◽  
C Elegans ◽  
Quantitative Analyses ◽  
Linear Sections

AbstractComplex dendritic trees are a distinctive feature of neurons. Alterations to dendritic morphology are associated with developmental, behavioral and neurodegenerative diseases. The highly-arborized PVD neuron of C. elegans serves as a model to study dendritic patterning; however, quantitative, objective and automated analyses of PVD morphology are missing. Here, we present a method for neuronal feature extraction, based on deep-learning and fitting algorithms. The extracted neuronal architecture is represented by a database of structural elements for abstracted analysis. We obtain excellent automatic tracing of PVD trees and uncover that dendritic junctions are unevenly distributed. Surprisingly, these junctions are three-way-symmetrical on average, while dendritic processes are arranged orthogonally. We quantify the effect of mutations in git-1, a regulator of dendritic spine formation, on PVD morphology and discover a localized reduction in junctions. Our findings shed new light on PVD architecture, demonstrating the effectiveness of our objective analyses of dendritic morphology and suggest molecular control mechanisms.Author SummaryNerve cells (neurons) collect input signals via branched cellular projections called dendrites. A major aspect of the study of neurons, dating back for over 100 years, involves the characterization of neuronal shapes and of their dendritic processes.Here, we present an algorithmic approach for detection and classification of the tree-like dendrites of the PVD neuron in C. elegans worms. A key feature of our approach is to represent dendritic trees by a sets of fundamental shape elements, such as junctions and linear sections. By analyzing this dataset, we discovered several novel structural features. We have found that the junctions connecting branched dendrites have a three-way-symmetry, although the dendrites are arranged in a crosshatch pattern; and that the distribution of junctions varies across distinct sub-classes of the PVD’s dendritic tree. We further quantified subtle morphological effects due to mutations in git-1 gene, a known regulator of dendritic spines. Our findings suggest molecular mechanisms for dendritic shape regulation and may help direct new avenues of research.

scholarly journals A multicellular rosette-mediated collective dendrite extension

2018 ◽  
Author(s):  
Li Fan ◽  
Ismar Kovacevic ◽  
Maxwell Heiman ◽  
Zhirong Bao
Keyword(s):  
Adhesion Molecules ◽  
Molecular Mechanisms ◽  
Neural Circuits ◽  
Sensory Nerve ◽  
Neuronal Cell ◽  
Sensory Organ ◽  
Neurite Extension ◽  
C Elegans ◽  
Neuronal Cell Bodies

Coordination of neurite morphogenesis with surrounding tissues is crucial to the establishment of neural circuits, but the underlying cellular and molecular mechanisms remain poorly understood. We show that neurons in a C. elegans sensory organ, called the amphid, undergo a collective dendrite extension to initiate formation of the sensory nerve. The amphid neurons first assemble into a multicellular rosette. The vertex of the rosette, which becomes the dendrite tips, is attached to the anteriorly migrating epidermis and carried to the sensory depression, extruding the dendrites away from the neuronal cell bodies. Multiple adhesion molecules including DYF-7, SAX-7, HMR-1 and DLG-1 function redundantly in rosette-to-epidermis attachment. PAR-6 is localized to the rosette vertex and dendrite tips, and promotes DYF-7 localization and dendrite extension. Our results suggest a collective mechanism of neurite extension that is distinct from the classical pioneer-follower model and highlight the role of mechanical cues from surrounding tissues in shaping neurites.

scholarly journals Trans-Axonal Signaling in Neural Circuit Wiring

2020 ◽  
Vol 21 (14) ◽  
pp. 5170 ◽  
Author(s):  
Olivia Spead ◽  
Fabienne E. Poulain
Keyword(s):  
Molecular Mechanisms ◽  
Neural Circuits ◽  
Neural Circuit ◽  
Target Selection ◽  
Synaptic Connectivity ◽  
Recent Advances ◽  
Complex Process ◽  
Circuit Formation

The development of neural circuits is a complex process that relies on the proper navigation of axons through their environment to their appropriate targets. While axon–environment and axon–target interactions have long been known as essential for circuit formation, communication between axons themselves has only more recently emerged as another crucial mechanism. Trans-axonal signaling governs many axonal behaviors, including fasciculation for proper guidance to targets, defasciculation for pathfinding at important choice points, repulsion along and within tracts for pre-target sorting and target selection, repulsion at the target for precise synaptic connectivity, and potentially selective degeneration for circuit refinement. This review outlines the recent advances in identifying the molecular mechanisms of trans-axonal signaling and discusses the role of axon–axon interactions during the different steps of neural circuit formation.

How do histone modifications contribute to transgenerational epigenetic inheritance in C. elegans?

2020 ◽  
Vol 48 (3) ◽  
pp. 1019-1034 ◽  
Author(s):  
Rachel M. Woodhouse ◽  
Alyson Ashe
Keyword(s):  
Histone Modifications ◽  
Molecular Mechanisms ◽  
Epigenetic Inheritance ◽  
Nematode Caenorhabditis Elegans ◽  
Histone Methyltransferases ◽  
Transgenerational Epigenetic Inheritance ◽  
C Elegans ◽  
Recent Developments ◽  
Gene Regulatory

Gene regulatory information can be inherited between generations in a phenomenon termed transgenerational epigenetic inheritance (TEI). While examples of TEI in many animals accumulate, the nematode Caenorhabditis elegans has proven particularly useful in investigating the underlying molecular mechanisms of this phenomenon. In C. elegans and other animals, the modification of histone proteins has emerged as a potential carrier and effector of transgenerational epigenetic information. In this review, we explore the contribution of histone modifications to TEI in C. elegans. We describe the role of repressive histone marks, histone methyltransferases, and associated chromatin factors in heritable gene silencing, and discuss recent developments and unanswered questions in how these factors integrate with other known TEI mechanisms. We also review the transgenerational effects of the manipulation of histone modifications on germline health and longevity.

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.

scholarly journals Gene regulatory networks controlling differentiation, survival, and diversification of hypothalamic Lhx6-expressing GABAergic neurons

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Dong Won Kim ◽  
Kai Liu ◽  
Zoe Qianyi Wang ◽  
Yi Stephanie Zhang ◽  
Abhijith Bathini ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Gabaergic Neurons ◽  
Zona Incerta ◽  
Long Distance ◽  
Hypothalamic Neurons ◽  
Cortical Interneuron ◽  
Tangential Migration ◽  
Innate Behaviors

AbstractGABAergic neurons of the hypothalamus regulate many innate behaviors, but little is known about the mechanisms that control their development. We previously identified hypothalamic neurons that express the LIM homeodomain transcription factor Lhx6, a master regulator of cortical interneuron development, as sleep-promoting. In contrast to telencephalic interneurons, hypothalamic Lhx6 neurons do not undergo long-distance tangential migration and do not express cortical interneuronal markers such as Pvalb. Here, we show that Lhx6 is necessary for the survival of hypothalamic neurons. Dlx1/2, Nkx2-2, and Nkx2-1 are each required for specification of spatially distinct subsets of hypothalamic Lhx6 neurons, and that Nkx2-2+/Lhx6+ neurons of the zona incerta are responsive to sleep pressure. We further identify multiple neuropeptides that are enriched in spatially segregated subsets of hypothalamic Lhx6 neurons, and that are distinct from those seen in cortical neurons. These findings identify common and divergent molecular mechanisms by which Lhx6 controls the development of GABAergic neurons in the hypothalamus.

scholarly journals Polymodal Functionality of C. elegans OLL Neurons in Mechanosensation and Thermosensation

2021 ◽  
Author(s):  
Yuedan Fan ◽  
Wenjuan Zou ◽  
Jia Liu ◽  
Umar Al-Sheikh ◽  
Hankui Cheng ◽  
...  
Keyword(s):  
Glutamate Receptor ◽  
Sensory Neurons ◽  
Molecular Mechanisms ◽  
Temperature Sensitive ◽  
Cold Sensation ◽  
Cold Response ◽  
C Elegans ◽  
Sensory Modalities ◽  
A Cell ◽  
Bona Fide

AbstractSensory modalities are important for survival but the molecular mechanisms remain challenging due to the polymodal functionality of sensory neurons. Here, we report the C. elegans outer labial lateral (OLL) sensilla sensory neurons respond to touch and cold. Mechanosensation of OLL neurons resulted in cell-autonomous mechanically-evoked Ca2+ transients and rapidly-adapting mechanoreceptor currents with a very short latency. Mechanotransduction of OLL neurons might be carried by a novel Na+ conductance channel, which is insensitive to amiloride. The bona fide mechano-gated Na+-selective degenerin/epithelial Na+ channels, TRP-4, TMC, and Piezo proteins are not involved in this mechanosensation. Interestingly, OLL neurons also mediated cold but not warm responses in a cell-autonomous manner. We further showed that the cold response of OLL neurons is not mediated by the cold receptor TRPA-1 or the temperature-sensitive glutamate receptor GLR-3. Thus, we propose the polymodal functionality of OLL neurons in mechanosensation and cold sensation.

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