Comprehensive analysis of the C. elegans connectome reveals novel circuits and functions of previously unstudied neurons.

Despite decades of research on the Caenorhabditis elegans nervous system based on an anatomical description of synaptic connectivity, the circuits underlying behavior remain incompletely described and the functions of many neurons are still unknown. Updated and more complete chemical and gap junction connectomes of both adult sexes covering the entire animal including the muscle end organ have become available recently. Here, these are analyzed to gain insight into the overall structure of the connectivity network and to suggest functions of individual neuron classes.

FUNCTIONS OF NEURONS FROM SYNAPTIC CONNECTIVITY.

Despite decades of research on the nervous system based on an anatomical description of synaptic connectivity, the circuits underlying behavior remain incompletely described and the functions of many neurons are still unknown. Updated and more complete chemical and gap junction connectomes of both adult sexes covering the entire animal including the muscle end organ have become available recently. Here these are analyzed to gain insight into the overall structure of the connectivity network and to suggest functions of individual neuron classes.

Prediction of interactions between cell surface proteins by machine learning.

Cells detect changes in their external environments or communicate with each other through proteins on their surfaces. These cell surface proteins form a complicated network of interactions in order to fulfill their functions. The interactions between cell surface proteins are highly dynamic and, thus, challenging to detect using traditional experimental techniques.

Prediction of Interactions between Cell Surface Proteins by Machine Learning.

Cells detect changes of external environments or communicate with each other through proteins on their surfaces. These cell surface proteins form a complicated network of interactions in order to fulfill their functions. The interactions between cell surface proteins are highly dynamic and thus challenging to detect using traditional experimental techniques.

The synaptic organization in the neural network suggests significant local compartmentalized computations.

Neurons are characterized by elaborate tree-like dendritic structures that support local computations by integrating multiple inputs from upstream presynaptic neurons. It is less clear whether simple neurons, consisting of a few or even a single neurite, may perform local computations as well. To address this question, we focused on the compact neural network of  animals for which the full wiring diagram is available, including the coordinates of individual synapses.

Function of cell adhesion molecules in differentiation of ray sensory neurons in C. elegans.

For proper functioning of the nervous system, it is crucial that neurons find their appropriate partners and build the correct neural connection patterns. Although cell adhesion molecules (CAMs) have been studied for many years as essential players in neural connections, we have yet to unravel the code by which CAMs encode synaptic specificity. We analyzed the effects of mutations in CAM genes on the morphology and synapses of a set of sensory neurons in the Caenorhabditis elegans male tail.

Methods for analyzing neuronal structure and activity in Caenorhabditis elegans.

The model research animal Caenorhabditis elegans has unique properties making it particularly advantageous for studies of the nervous system. The nervous system is composed of a stereotyped complement of neurons connected in a consistent manner. Here, we describe methods for studying nervous system structure and function.

A multi-scale brain map derived from whole-brain volumetric reconstructions.

Animal nervous system organization is crucial for all body functions and its disruption can lead to severe cognitive and behavioural impairment. This organization relies on features across scales-from the localization of synapses at the nanoscale, through neurons, which possess intricate neuronal morphologies that underpin circuit organization, to stereotyped connections between different regions of the brain. The sheer complexity of this organ means that the feat of reconstructing and modelling the structure of a complete nervous system that is integrated across all of these scales has yet to be achieved.

Direct glia-to-neuron transdifferentiation gives rise to a pair of male-specific neurons that ensure nimble male mating.

Sexually dimorphic behaviours require underlying differences in the nervous system between males and females. The extent to which nervous systems are sexually dimorphic and the cellular and molecular mechanisms that regulate these differences are only beginning to be understood. We reveal here a novel mechanism by which male-specific neurons are generated in through the direct transdifferentiation of sex-shared glial cells.

The connectome of the Caenorhabditis elegans pharynx.

Detailed anatomical maps of individual organs and entire animals have served as invaluable entry points for ensuing dissection of their evolution, development, and function. The pharynx of the nematode Caenorhabditis elegans is a simple neuromuscular organ with a self-contained, autonomously acting nervous system, composed of 20 neurons that fall into 14 anatomically distinct types. Using serial electron micrograph (EM) reconstruction, we re-evaluate here the connectome of the pharyngeal nervous system, providing a novel and more detailed view of its structure and predicted function.

Concurrency and reachability in treelike temporal networks.

Network properties govern the rate and extent of various spreading processes, from simple contagions to complex cascades. Recently, the analysis of spreading processes has been extended from static networks to temporal networks, where nodes and links appear and disappear. We focus on the effects of accessibility, whether there is a temporally consistent path from one node to another, and reachability, the density of the corresponding accessibility graph representation of the temporal network.

Expressional artifact caused by a co-injection marker rol-6 in C. elegans.

In transgenic research, selection markers have greatly facilitated the generation of transgenic animals. A prerequisite for a suitable selection marker to be used along with a test gene of interest is that the marker should not affect the phenotype of interest in transformed animals. One of the most common selection markers used in C.

Map equation with metadata: Varying the role of attributes in community detection.

Much of the community detection literature studies structural communities, communities defined solely by the connectivity patterns of the network. Often networks contain additional metadata which can inform community detection such as the grade and gender of students in a high school social network. In this work, we introduce a tuning parameter to the content map equation that allows users of the Infomap community detection algorithm to control the metadata's relative importance for identifying network structure.

Neural Circuits of Sexual Behavior in Caenorhabditis elegans.

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.

Synaptogenesis Is Modulated by Heparan Sulfate in .

The 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 It is composed of sequential steps that are governed by > 3000 chemical connections.

Post-Processing Partitions to Identify Domains of Modularity Optimization.

We introduce the Convex Hull of Admissible Modularity Partitions (CHAMP) algorithm to prune and prioritize different network community structures identified across multiple runs of possibly various computational heuristics. Given a set of partitions, CHAMP identifies the domain of modularity optimization for each partition-i.e.

Neural Circuitry That Mediates Behavior Governing the Tradeoffs Between Survival and Reproduction in Caenorhabditis elegans.

In all outcrossing sexual species there is a mechanism that brings two parents together. For animals, this reproductive requirement may at times conflict with other needs, such as foraging for food. This tension has been studied using the tiny (1 mm) nematode worm, Caenorhabditis elegans.

Multiple conserved cell adhesion protein interactions mediate neural wiring of a sensory circuit in .

Nervous system function relies on precise synaptic connections. A number of widely-conserved cell adhesion proteins are implicated in cell recognition between synaptic partners, but how these proteins act as a group to specify a complex neural network is poorly understood. Taking advantage of known connectivity in , we identified and studied cell adhesion genes expressed in three interacting neurons in the mating circuits of the adult male.

Gene Function Prediction Based on Developmental Transcriptomes of the Two Sexes in C. elegans.

We compare whole-animal RNA-seq transcriptomes for C. elegans males and hermaphrodites from the late L3 larval stage to young adulthood. During this interval, male sexual structures develop, including extensive neurogenesis and synaptogenesis that nearly doubles the size of the nervous system.

Analysis of Network Clustering Algorithms and Cluster Quality Metrics at Scale.

Overview: Notions of community quality underlie the clustering of networks. While studies surrounding network clustering are increasingly common, a precise understanding of the realtionship between different cluster quality metrics is unknown. In this paper, we examine the relationship between stand-alone cluster quality metrics and information recovery metrics through a rigorous analysis of four widely-used network clustering algorithms-Louvain, Infomap, label propagation, and smart local moving.

Connectomics, the Final Frontier.

How the synaptic connections in the nervous system are genetically encoded and formed during development remains an unsolved problem. The known connectivity of the nervous system of the nematode C. elegans provides an opportunity to search for the genes involved.

Palliative radiotherapy fractionation schedules prescribed are dependent on the distance a patient travels to receive treatment.

This study assessed the impact of the distance a patient travelled to the treatment centre on the use of single fraction RT for bone metastases. There was significant variability in the prescription of SFRT by distance at which the patient lives from a cancer centre (p<0.001).