Optogenetic analyses of neuronal networks that generate behavior in Caenorhabditis elegans

Alexander Gottschalk

doi:10.1515/nf-2020-0022

Abstract

Abstract In compact brains, circuits consisting of few neurons fulfill functions of entire brain systems in mammals. Thus, studying these small circuits can provide insights and guidelines also for the study of the human brain. We developed methods and approaches to use optogenetics in the nervous and neuromuscular system of the nematode Caenorhabditis elegans. These include single-cell expression and/or photoactivation of optogenetic tools, to control the function of individual neurons, and behavioral, electrophysiological or electron microscopic analyses of circuit function and synaptic transmission. We studied a number of circuits involved in locomotion, navigation and food searching; we addressed new genes in synaptic vesicle recycling, and we identified a novel pathway of neuromodulatory presynaptic plasticity. In our laboratory, support by the Schram foundation allowed me to explore new avenues of research especially during the early years of my career.

Highlights

The nematode Caenorhabditis elegans has a compact nervous system of 302 neurons, whose connectivity has been determined by serial electron microscopy (EM) in the 70s and 80s of the twentieth century, and the data were revisited last year (Cook et al, 2019; White et al, 1986)
Due to the compactness of the C. elegans nervous system, single neurons often need to fulfill the function of entire circuits in higher animals, though at a lower level of complexity
The function of individual C. elegans neurons was inferred from animals in which these neurons were eliminated by laser ablation and by observing the altered behaviors that resulted from the loss of the neuron

Summary

Introduction

The nematode Caenorhabditis elegans has a compact nervous system of 302 neurons, whose connectivity has been determined by serial electron microscopy (EM) in the 70s and 80s of the twentieth century, and the data were revisited last year (Cook et al, 2019; White et al, 1986). New connectomes, acquired with modern EM techniques, across development of the animal, have been determined, providing comprehensive ‘wiring diagrams’ of the C. elegans brain (Witvliet et al, 2020). This information forms a basis to the understanding of the function of neuronal circuits in the generation of behavior of ‘the worm.’. Due to the compactness of the C. elegans nervous system, single neurons often need to fulfill the function of entire circuits in higher animals, though at a lower level of complexity. Optogenetic methods allow the interference with neuronal function, for example, via light-activated anion channels or

Gottschalk

Conclusion