title: Temporally precise labeling and control of neuromodulatory circuits in the mammalian brain.
abstract: Few tools exist to visualize and manipulate neurons that are targets of neuromodulators. We present iTango, a light- and ligand-gated gene expression system based on a light-inducible split tobacco etch virus protease. Cells expressing the iTango system exhibit increased expression of a marker gene in the presence of dopamine and blue-light exposure, both in vitro and in vivo. We demonstrated the iTango system in a behaviorally relevant context, by inducing expression of optogenetic tools in neurons under dopaminergic control during a behavior of interest. We thereby gained optogenetic control of these behaviorally relevant neurons. We applied the iTango system to decipher the roles of two classes of dopaminergic neurons in the mouse nucleus accumbens in a sensitized locomotor response to cocaine. Thus, the iTango platform allows for control of neuromodulatory circuits in a genetically and functionally defined manner with spatial and temporal precision.
authors.affiliation: Max Planck Florida Institute for Neuroscience, Jupiter, Florida, USA.|Department of Anatomy, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Dongmin
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Basic Neuroscience, University of Geneva, Geneva, Switzerland.
authors.forename: Meaghan
authors.initials: M
authors.lastname: Creed
authors.affiliation: Max Planck Florida Institute for Neuroscience, Jupiter, Florida, USA.
authors.forename: Kanghoon
authors.initials: K
authors.lastname: Jung
authors.affiliation: Department of Basic Neuroscience, University of Geneva, Geneva, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Stefanelli
authors.affiliation: Max Planck Florida Institute for Neuroscience, Jupiter, Florida, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Wendler
authors.affiliation: Max Planck Florida Institute for Neuroscience, Jupiter, Florida, USA.
authors.forename: Won Chan
authors.initials: WC
authors.lastname: Oh
authors.affiliation: Max Planck Florida Institute for Neuroscience, Jupiter, Florida, USA.
authors.forename: Neymi Layne
authors.initials: NL
authors.lastname: Mignocchi
authors.affiliation: Department of Basic Neuroscience, University of Geneva, Geneva, Switzerland.|Service of Neurology, Geneva University Hospital, Geneva, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Lüscher
authors.affiliation: Max Planck Florida Institute for Neuroscience, Jupiter, Florida, USA.|Max Planck Institute of Neurobiology, Martinsried, Germany.
authors.forename: Hyung-Bae
authors.initials: HB
authors.lastname: Kwon
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D001931:Brain Mapping / Q000379:methods; D004298:Dopamine / Q000378:metabolism* / Q000494:pharmacology; D010450:Endopeptidases / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects / Q000528:radiation effects; D057809:HEK293 Cells; D006801:Humans; D008024:Ligands; D008027:Light; D051379:Mice; D009434:Neural Pathways / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D062308:Optogenetics / Q000379:methods*; D010775:Photic Stimulation; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000235:genetics; D059629:Signal-To-Noise Ratio
chemical_list: D008024:Ligands; D017448:Receptors, Dopamine D2; D010450:Endopeptidases; C099488:TEV protease; D004298:Dopamine