Develop a "forward optogenetic" pipeline to generalize the screening of neuro-modulators

Our understanding of molecular framework involved in "sensory behaviors" (like chemo-, mechano-, osmo- or thermo-sensation) strongly benefited from efficient classical genetic screens identifying defective mutants in C. elegans. However, neuronal analysis have shown that several neural pathways are often acting in parallel, which limits the ability of classical genetic genetic screens to discover targets that are functioning in a single branch of redundant pathways. Furthermore, existing behavior screens cannot selectively address the functions of neurons for which specific stimuli are unavailable (like interneurons, located downstream in the circuit).

To circumvent these limitations, we are trying to create a "synthetic behavior paradigm". We will use transgenic animals expressing Channelrhodopsin (ChR2) in specific neurons, enabling their artificial stimulation with light and the generation of light-induced behaviors. We will mutagenize these animals and screen for mutants with defective light-induced behavior. In principle, this approach can be applied for any neuron that regulates behavior, and whose effect can be screened for.