Biology subjects

Emmons, S. W.

Publications and source records attributed to Emmons, S. W..

7 recordsLinked to original sources

bioRxiv2024

Function of C. elegans neurons from synaptic connectivity

Despite decades of research on the C. 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. Modularity analysis divides the connectome graph into ten communities that can be correlated with broad categories of behavior. A significant role of the body wall musculature end organ is emphasized as both a site of significant information convergence and as a source of sensory input in a feedback loop. Convergence of pathways for multisensory integration occurs throughout the network -- most interneurons have similar indegrees and outdegrees and hence disperse information as much as they aggregate it. New insights include description of a set of high degree interneurons connected by many gap junctions running through the ventral cord that may represent a previously unrecognized locus of information processing. There is an apparent mechanosensory and proprioceptive field covering the entire body formed by connectivity of the many mechanosensory neurons of multiple types to two interneurons with output connections across the nervous system. Several additional significant, previously unrecognized circuits and pathways are uncovered, some involving unstudied neurons. The insights are valuable for guiding theoretical investigation of network properties as well as experimental studies of the functions of individual neurons, groups of neurons, and circuits.

neuroscience↗

bioRxiv2022

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 C. elegans male tail. B-type ray sensory neurons express ten genes encoding CAMs. We examined the effect on axon trajectory and localization of presynaptic components in viable mutants of nine of these. We found axon trajectory defects in mutants of UNC-40/DCC, SAX-3/ROBO, and FMI-1/Flamingo/Celsr1. In none of the mutants was presence of presynaptic components in axons lost, and in several the level appeared to increase, suggesting possible accumulation. B-type sensory neurons fasciculate with a second type of ray sensory neuron, the A-type, in axon commissures. We found cell non-autonomous effects consistent with each promoting the trajectory of the other. Overall, single and multiple mutants of CAM genes had limited effects on ray neuron trajectories and accumulation of synaptic components.

genetics↗

bioRxiv2022

The synaptic organization in the C. elegans 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 if 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 C. elegans animals for which the full wiring diagram is available, including the coordinates of individual synapses. We find that the positions of the chemical synapses along the neurites are not randomly distributed, nor can they be explained by anatomical constraints. Instead, synapses tend to form clusters, an organization that supports local compartmentalized computations. In mutually-synapsing neurons, connections of opposite polarity cluster separately, suggesting that positive and negative feedback dynamics may be implemented in discrete compartmentalized regions along neurites. In triple-neuron circuits, the non-random synaptic organization may facilitate local functional roles, such as signal integration and coordinated activation of functionally-related downstream neurons. These clustered synaptic topologies emerge as a guiding principle in the network presumably to facilitate distinct parallel functions along a single neurite, effectively increasing the computational capacity of the neural network.

neuroscience↗

bioRxiv2020

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

Animal 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.

neuroscience↗

bioRxiv2019

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 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. Contrasting the previous classification of pharyngeal neurons into distinct inter- and motorneuron classes, we provide evidence that most pharyngeal neurons are also likely sensory neurons and most, if not all, pharyngeal neurons also classify as motorneurons. Together with the extensive cross-connectivity among pharyngeal neurons, which is more widespread than previously realized, the sensory-motor characteristics of most neurons define a shallow network architecture of the pharyngeal connectome. Network analysis reveals that the patterns of neuronal connections are organized into putative computational modules that reflect the known functional domains of the pharynx. Compared to the somatic nervous system, pharyngeal neurons both physically associate with a larger fraction of their neighbors and create synapses with a greater proportion of their neighbors. We speculate that the overall architecture of the pharyngeal nervous system may be reminiscent of the architecture of ancestral, primitive nervous systems.

neuroscience↗

bioRxiv2019

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. elegans transgenic approaches is the rol-6 co-injection marker, which induces a behavioral roller phenotype due to a cuticle defect but is not known to have other side effects. However, we found that the rol-6 co-injection marker can cause expression of GFP in the test sequence in a male-specific interneuron called CP09. We found that the rol-6 gene sequence included in the marker plasmid is responsible for this unwanted expression. Accordingly, the use of the rol-6 co-injection marker is not recommended when researchers intend to examine precise expression or perform functional studies especially targeting male C. elegans neurons. The rol-6 sequence region we identified can be used to drive a specific expression in CP09 neuron for future research.

genetics↗

bioRxiv2018

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

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.

developmental biology↗