From synapse to behavior: Optogenetic tools for the investigation of the Caenorhabditis elegans nervous system

Introduction Optogenetics, though still only a decade old as a field, has revolutionized research in neuroscience and cell biology. It allows for the non-invasive, spatiotemporally precise and genetically targeted light control of neural activity. The optogenetic actuators or the genetically encoded light-addressable elements mediate the light-driven manipulation of membrane potential, intracellular signaling, neuronal network activity and behavior (Fenno, Yizhar and Deisseroth, 2011; Dugué, Akemann and Knöpfel, 2012; Husson, Gottschalk and Leifer, 2013; Fang-Yen et al., 2015). The transparent and genetically amenable nematode Caenorhabditis elegans is a versatile model organism that has been used extensively in the fields of molecular, cellular and systems neuroscience. It possesses a nervous system comprising 302 neurons (in adult hermaphrodites), which has been anatomically mapped to the synapse resolution (White et al., 1986). This complete “wiring diagram” of the nervous system is highly conserved between individual C. elegans worms, which are eutelic organisms (having a fixed number of somatic cells). Despite a seemingly simple nervous system comprising 7000 synapses in between 302 neurons and muscle cells, C. elegans exhibits a rich repertoire of quantifiable behavior (de Bono and Maricq, 2005; Sengupta and Samuel, 2009; Yemini et al., 2013). It can respond to a variety of sensory stimuli, such as chemical, mechanical, thermal, gaseous and magnetic ones. It also exhibits habituation and simple forms of associative learning (Ardiel and Rankin, 2010). Furthermore, there is a remarkable level of conservation in the genes and neurochemistry of C. elegans and mammals. Its optical transparency and genetic tractability make C. elegans a highly attractive model system for the use of optogenetics when performing neuroscientific investigations (Xu and Kim, 2011). In fact, it was the first animal in which optogenetic tools based on microbial rhodopsins were successfully implemented and behavior was remotely controlled using them (Nagel et al., 2005; Zhang et al., 2007). Since then, C. elegans has been a model of choice for the development and application of novel optogenetic tools and techniques. The combination of optogenetic actuators with optogenetic reporters of neural activity (genetically encoded calcium and voltage indicators) are providing hitherto unprecedented access to the dissection of neural circuits and behavior in C. elegans (Husson et al., 2012b; Akerboom et al., 2013; Flytzanis et al., 2014; Wabnig et al., 2015).