Wired for insight-recent advances in Caenorhabditis elegans neural circuits

Abstract

The completion of Caenorhabditis elegans connectomics four decades ago has long guided mechanistic investigation of neuronal circuits. Recent technological advances in microscopy and computation programs have aided re-examination of this connectomics, expanding our knowledge by both uncovering previously unreported synaptic connections and also generating models for neural networks underlying behaviors. Combining molecular information from single cell transcriptomes with elegant tools for cell-specific manipulation has further enhanced the ability to precisely investigate individual neurons in behaving animals. This mini-review aims to provide an overview of new information on connectomics and progress toward a molecular atlas of C. elegans nervous system, and discuss emerging findings on neuronal circuits.

Keywords: Chemogenetic tools; Connectomics; Genomics; Locomotion pattern generator; Microscopy; Motor circuit; Neuromodulation; Neuro–gut axis; Optogenetic tools; Super-resolution imaging.

Figure 1.. C. elegans nervous system and circuit mechanisms for locomotion

A. Graphic representation of the entire nervous system. Dots illustrate neuronal soma, lines nerve processes. Head ganglia consists of majority sensory neurons and interneurons (IN), including premotor command neurons. Tail ganglia consists of sensory neurons and INs. Ventral nerve cord consists of eight classes of motor neurons (MNs) organized in repetitive units from head to tail, and connects to dorsal nerve cord through circumferential commissures (verticle lines). Touch receptor neurons (TRN) sense and transduce mechanic stimuli to pre-motor command neurons to initiate forward or backward movement. Drawings are modified from the art work provided by Erik M. Jorgensen, with permission. B. Schematics of the C. elegans motor circuit components and connectivity in (i) wild type animals and (ii, iii) upon ablation of respective neuronal populations (as faded color), with a snap shot of representative body posture exhibited by adult worm shown below. Hexagons and circles represent pre-motor interneurons and ventral cord MNs, respectively. Orange and blue denote components of the forward and reversal motor circuit, respectively. Taupe denotes neurons that participate both forward and backward locomotion. Reproduced from Figure 1A in Gao et al (2018), with permission. C. Ventral cord AS MNs asymmetrically regulate dorso-ventral bending during forward and backward locomotion, modified from Figure 7 in Tolstenkov et al (2018) with permission. Left illustration shows functional connections between pre-motor interneuron AVA and AVB with AS MNs, which synapse onto ventral GABAergic VD MNs to inhibit body muscles. Right illustration shows interconnections and functional roles of AS MNs and other VNC MNs during the propagation of the undulatory wave along the body. Cholinergic (orange) and GABAergic (blue) cell types are indicated.

Figure 2.. Summary of recent findings within the C. elegans neuro-gut axis

Animals ingest bacteria (yellow) that sometimes colonize the gut. Microbial colonization of pathogenic bacteria may induce intestinal bloating, which induces NPR-1 neuropeptide signaling to promote aversion of the pathogenic bacteria (red signaling pathway), based on Singh and Aballay (2019a). Non-pathogenic colonizing Providencia strains produce tyramine (L-Tyr) that may be converted to octopamine within the worm and signal through the octopamine receptor (OCTR-1) expressed by ASH sensory neurons to modulate avoidance of octanol and influence food choice (green signaling pathway), based on O’Donnell et al (2020). Sensation of the odor 2-butanone inhibits the AWC_on chemosensory neuron, which inhibits AIY interneuron from releasing FLP-1/FMRFamide neuropeptides that can signal to the intestine through the NPR-4/NPY receptor, SGK-1/SGK1 kinase, and DAF-16/FOXO transcription factor to control lipid homeostasis (purple pathway), based on Mutlu et al (2020).