title: Inhibitory luminopsins: genetically-encoded bioluminescent opsins for versatile, scalable, and hardware-independent optogenetic inhibition.
abstract: Optogenetic techniques provide an unprecedented ability to precisely manipulate neural activity in the context of complex neural circuitry. Although the toolbox of optogenetic probes continues to expand at a rapid pace with more efficient and responsive reagents, hardware-based light delivery is still a major hurdle that limits its practical use in vivo. We have bypassed the challenges of external light delivery by directly coupling a bioluminescent light source (a genetically encoded luciferase) to an inhibitory opsin, which we term an inhibitory luminopsin (iLMO). iLMO was shown to suppress action potential firing and synchronous bursting activity in vitro in response to both external light and luciferase substrate. iLMO was further shown to suppress single-unit firing rate and local field potentials in the hippocampus of anesthetized rats. Finally, expression of iLMO was scaled up to multiple structures of the basal ganglia to modulate rotational behavior of freely moving animals in a hardware-independent fashion. This novel class of optogenetic probes demonstrates how non-invasive inhibition of neural activity can be achieved, which adds to the versatility, scalability, and practicality of optogenetic applications in freely behaving animals.
authors.affiliation: Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA.|Department of Neurosurgery, Emory University, Atlanta, GA.
authors.forename: Jack K
authors.initials: JK
authors.lastname: Tung
authors.affiliation: Department of Neurosurgery, Emory University, Atlanta, GA.
authors.forename: Claire-Anne
authors.initials: CA
authors.lastname: Gutekunst
authors.affiliation: Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA.|Department of Neurosurgery, Emory University, Atlanta, GA.|Department of Neurology, Emory University, Atlanta, GA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Gross
mesh_terms: D000200:Action Potentials; D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism; D001522:Behavior, Animal; D002460:Cell Line; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000528:radiation effects; D006801:Humans; D008027:Light; D008156:Luciferases / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000378:metabolism; D055355:Opsins / Q000235:genetics* / Q000378:metabolism; D062308:Optogenetics / Q000379:methods; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D055355:Opsins; D011993:Recombinant Fusion Proteins; D008156:Luciferases