14125 2011 eng e18766 4 6 article 1 2016-12-01 -- -- Optogenetic Long-Term Manipulation of Behavior and Animal Development Channelrhodopsin-2 (ChR2) is widely used for rapid photodepolarization of neurons, yet, as it requires high-intensity blue light for activation, it is not suited for long-term in vivo applications, e. g. for manipulations of behavior, or photoactivation of neurons during development. We used "slow" ChR2 variants with mutations in the C128 residue, that exhibit delayed off-kinetics and increased light sensitivity in Caenorhabditis elegans. Following a 1 s light pulse, we could photodepolarize neurons and muscles for minutes (and with repeated brief stimulation, up to days) with low-intensity light. Photoactivation of ChR2(C128S) in command interneurons elicited long-lasting alterations in locomotion. Finally, we could optically induce profound changes in animal development: Long-term photoactivation of ASJ neurons, which regulate larval growth, bypassed the constitutive entry into the "dauer" larval state in daf-11 mutants. These lack a guanylyl cyclase, which possibly renders ASJ neurons hyperpolarized. Furthermore, photostimulated ASJ neurons could acutely trigger dauer-exit. Thus, slow ChR2s can be employed to long-term photoactivate behavior and to trigger alternative animal development. PLoS ONE 10.1371/journal.pone.0018766 urn:nbn:de:bvb:20-opus-141250 PLoS ONE 6(4): e18766. doi:10.1371/journal.pone.0018766 Christian Schultheis Jana Fiona Liewald Ernst Bamberg Georg Nagel Alexander Gottschalk eng uncontrolled Nematode Caenorhabditis-elegans eng uncontrolled C-elegans eng uncontrolled Millisecond-timescale eng uncontrolled Chemosensory neurons eng uncontrolled Glutamate-receptor eng uncontrolled Larval development eng uncontrolled Optical control eng uncontrolled Dauer formation eng uncontrolled Channelrhodopsin-2 eng uncontrolled Pheromone Biowissenschaften; Biologie open_access Julius-von-Sachs-Institut für Biowissenschaften Universität Würzburg https://opus.bibliothek.uni-wuerzburg.de/files/14125/104_Schultheis_PLOS-ONE.PDF