title: Optogenetic long-term manipulation of behavior and animal development.
abstract: 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.
authors.affiliation: Institute of Biochemistry, Goethe-University, Frankfurt, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Schultheis
authors.forename: Jana Fiona
authors.initials: JF
authors.lastname: Liewald
authors.forename: Ernst
authors.initials: E
authors.lastname: Bamberg
authors.forename: Georg
authors.initials: G
authors.lastname: Nagel
authors.forename: Alexander
authors.initials: A
authors.lastname: Gottschalk
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D008027:Light; D008124:Locomotion; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D012243:Rhodopsin / Q000235:genetics / Q000502:physiology*
chemical_list: D029742:Caenorhabditis elegans Proteins; D009419:Nerve Tissue Proteins; D012243:Rhodopsin