Novel Technological Advances in Functional Connectomics in C. elegans

Abstract

The complete structure and connectivity of the Caenorhabditis elegans nervous system (“mind of a worm”) was first published in 1986, representing a critical milestone in the field of connectomics. The reconstruction of the nervous system (connectome) at the level of synapses provided a unique perspective of understanding how behavior can be coded within the nervous system. The following decades have seen the development of technologies that help understand how neural activity patterns are connected to behavior and modulated by sensory input. Investigations on the developmental origins of the connectome highlight the importance of role of neuronal cell lineages in the final connectivity matrix of the nervous system. Computational modeling of neuronal dynamics not only helps reconstruct the biophysical properties of individual neurons but also allows for subsequent reconstruction of whole-organism neuronal network models. Hence, combining experimental datasets with theoretical modeling of neurons generates a better understanding of organismal behavior. This review discusses some recent technological advances used to analyze and perturb whole-organism neuronal function along with developments in computational modeling, which allows for interrogation of both local and global neural circuits, leading to different behaviors. Combining these approaches will shed light into how neural networks process sensory information to generate the appropriate behavioral output, providing a complete understanding of the worm nervous system.

A Weighted Network Analysis Framework for the Hourglass Effect — and its Application in the C. Elegans Connectome

“…However, in the case of the male connectome, the sex-specific neurons form the majority of the core nodes. This is in line with the observations from previous studies that the pruning of synapses, that occurs at sexual maturation, affects a lot of sensorimotor pathways leading to a sexually dimorphic neuronal connectivity in the organism (DiLoreto et al, 2019). Moreover, previous work has found that the posterior nervous system in the males gets enlarged to support mating behavior, adding about 30% more neurons with parallel pathways and complex connectivity, matching that of the whole nervous system of the hermaphrodite (Jarrell et al, 2012).…”

The Role of Ca2+ Signaling in Aging and Neurodegeneration: Insights from Caenorhabditis elegans Models

“…The first dynamic cytosolic [Ca 2+ ] measurements were obtained in 2000 using a genetically-encoded Ca 2+ indicator expressed in pharyngeal muscle [114]. Since then, a variety of fluorescent Ca 2+ sensors have been used to monitor [Ca 2+ ] in pharynx, vulva, and body wall muscles, as well as in several kind of neurons [115,116], and also in subcellular compartments such as mitochondria [117]. These studies have made it possible to monitor the muscle or neuronal dynamics in live worms, either in resting conditions or after pharmacological or optogenetic stimulation.…”

Computing Temporal Sequences Associated With Dynamic Patterns on the C. elegans Connectome

“…Although the organism's connectome has been known for decades, how neurons functionally interact in the context of the entire network and how the resultant dynamics regulates participating neurons is not fully understood (Bargmann, 2012 ; Bargmann and Marder, 2013 ; Larson et al, 2018 ). A recent tend in C. elegans research is to study the dynome (Kopell et al, 2014 ; DiLoreto et al, 2019 ; Towlson et al, 2018 ), rather than drawing inferences from just the structural connectivity of the network (Towlson et al, 2013 ; Varshney et al, 2011 ; Sabrin et al, 2019 ).…”