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Abstract:

Light-gated ion channels or pumps such as the blue light-activated depolarizing Channelrhodopsin (ChR2) and the yellow light-driven hyperpolarizing Halorhodopsin (HR) allow optical activation or inhibition in muscles and neurons of live and behaving C. elegans (Zhang et al., 2007). Furthermore, inward currents evoked by either ChR2 or HR, as well as muscle currents in response to activating ChR2 in motor neurons, can be directly measured by electrophysiology, while photo-evoked body contraction or elongation of the animal could be monitored at the behavioural level (Nagel et al., 2005; Liewald et al., 2008). These state-of-the-art technologies pave the way for further functional dissection of individual neuronal networks in a detail that is not possible in higher organisms. Doing so, we are investigating some defined neuropeptidergic signalling pathways. Neuropeptide release can be triggered by photo-activating the respective neurons in an acute fashion while effects on behaviour can be observed at the same time. This way, we can correlate neuropeptide action with acute behavioural changes or effects, about which very limited knowledge is currently available in any system. While higher organisms display millions of contributing neurons, only a handful of neurons take part in individual neuronal networks in C. elegans. This opens the possibility to study the contribution of each neuron to the function of a small network, for example involved in nociception. The huge advantage of our optogenetics tools is that we can specifically stimulate the sensory input neurons, while other potentially contributing neurons are kept silent. The involvement of different ion channels, receptors or neurotransmitters can be assessed by using different genetic backgrounds, while the physiological properties of each individual neuron will be monitored by electrophysiology. Liewald JF, Brauner M, Stephens GJ, Bouhours M, Schultheis C, Zhen M, and Gottschalk A (2008) Optogenetic analysis of synaptic function. Nat Methods, 5, 895-902. Nagel G, Brauner M, Liewald JF, Adeishvili N, Bamberg E, and Gottschalk A (2005) Light activation of channelrhodopsin-2 in excitable cells of Caenorhabditis elegans triggers rapid behavioral responses. Curr Biol, 15, 2279-2284. Zhang F, Wang LP, Brauner M, Liewald JF, Kay K, Watzke N, Wood PG, Bamberg E, Nagel G, Gottschalk A, and Deisseroth K (2007) Multimodal fast optical interrogation of neural circuitry. Nature, 446, 633-639.