Optogenetic manipulation of neural activity in C. elegans: From synapse to circuits and behaviour

Abstract

The emerging field of optogenetics allows for optical activation or inhibition of excitable cells. In 2005, optogenetic proteins were expressed in the nematode Caenorhabditis elegans for the first time. Since then, C. elegans has served as a powerful platform upon which to conduct optogenetic investigations of synaptic function, circuit dynamics and the neuronal basis of behaviour. The C. elegans nervous system, consisting of 302 neurons, whose connectivity and morphology has been mapped completely, drives a rich repertoire of behaviours that are quantifiable by video microscopy. This model organism's compact nervous system, quantifiable behaviour, genetic tractability and optical accessibility make it especially amenable to optogenetic interrogation. Channelrhodopsin-2 (ChR2), halorhodopsin (NpHR/Halo) and other common optogenetic proteins have all been expressed in C. elegans. Moreover, recent advances leveraging molecular genetics and patterned light illumination have now made it possible to target photoactivation and inhibition to single cells and to do so in worms as they behave freely. Here, we describe techniques and methods for optogenetic manipulation in C. elegans. We review recent work using optogenetics and C. elegans for neuroscience investigations at the level of synapses, circuits and behaviour.

A Transparent window into biology: A primer on Caenorhabditis elegans

“…Furthermore, mapping of cell-cell and synaptic contacts can be accomplished by expressing complementary fragments of GFP in different cells (GRASP; Feinberg et al 2008). Transparency also means that optogenetic tools, which alter the activity of individual neurons, are particularly effective in C. elegans (Husson et al 2013). In all of these experiments, greater control of the animal's position and environment can be accomplished by microfluidic devices in which individual worms are mounted in custom-designed channels allowing the application of various compounds or other agents while simultaneously monitoring fluorescent readout of gene regulation or electrophysiological activity by microscopy (Lockery 2007;San-Miguel and Lu 2013).…”

Dual Color Neural Activation and Behavior Control with Chrimson and CoChR in Caenorhabditis elegans

“…A higher sensitivity constitutes an important advantage when targeting neurons for which strong promoters are not available. ChR2 has been commonly activated with light intensities between 500 and 5000 W/m 2 (Husson et al 2013). However, blue light stimuli above 500 W/m 2 elicit an intrinsic, lite-1-dependent photophobic response (Edwards et al 2008).…”

“…C. elegans is an attractive model to decipher the nervous system functioning in vivo, notably because of its fully mapped nervous system, easily quantifiable behaviors, and the availability of powerful genetic tools (Schafer 2005). Moreover, its transparent body and its comparatively low intrinsic responsiveness to light make it an ideal model for optogenetics approaches (see Husson et al 2013 for a review).…”

Mechanosensation circuitry in Caenorhabditis elegans: A focus on gentle touch

“…Conversely, expression of a light-activated cation pump, i.e. channelrhodopsin (ChR2), stimulates neurons [41,48,57]. Optogenetic inactivation of RIM triggered spontaneous reversals in worms.…”