title: Biophysical constraints of optogenetic inhibition at presynaptic terminals.
abstract: We investigated the efficacy of optogenetic inhibition at presynaptic terminals using halorhodopsin, archaerhodopsin and chloride-conducting channelrhodopsins. Precisely timed activation of both archaerhodopsin and halorhodpsin at presynaptic terminals attenuated evoked release. However, sustained archaerhodopsin activation was paradoxically associated with increased spontaneous release. Activation of chloride-conducting channelrhodopsins triggered neurotransmitter release upon light onset. Thus, the biophysical properties of presynaptic terminals dictate unique boundary conditions for optogenetic manipulation.
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Mathias
authors.initials: M
authors.lastname: Mahn
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Matthias
authors.initials: M
authors.lastname: Prigge
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Shiri
authors.initials: S
authors.lastname: Ron
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Rivka
authors.initials: R
authors.lastname: Levy
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Ofer
authors.identifier: http://orcid.org/0000-0003-4228-1448
authors.initials: O
authors.lastname: Yizhar
mesh_terms: D000818:Animals; D055592:Biophysical Phenomena / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D057809:HEK293 Cells; D025602:Halorhodopsins / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009433:Neural Inhibition / Q000502:physiology*; D062308:Optogenetics / Q000379:methods*; D009924:Organ Culture Techniques; D017729:Presynaptic Terminals / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D025602:Halorhodopsins