title: Selective optical control of synaptic transmission in the subcortical visual pathway by activation of viral vector-expressed halorhodopsin.
abstract: The superficial layer of the superior colliculus (sSC) receives visual inputs via two different pathways: from the retina and the primary visual cortex. However, the functional significance of each input for the operation of the sSC circuit remains to be identified. As a first step toward understanding the functional role of each of these inputs, we developed an optogenetic method to specifically suppress the synaptic transmission in the retino-tectal pathway. We introduced enhanced halorhodopsin (eNpHR), a yellow light-sensitive, membrane-targeting chloride pump, into mouse retinal ganglion cells (RGCs) by intravitreously injecting an adeno-associated virus serotype-2 vector carrying the CMV-eNpHR-EYFP construct. Several weeks after the injection, whole-cell recordings made from sSC neurons in slice preparations revealed that yellow laser illumination of the eNpHR-expressing retino-tectal axons, putatively synapsing onto the recorded cells, effectively inhibited EPSCs evoked by electrical stimulation of the optic nerve layer. We also showed that sSC spike activities elicited by visual stimulation were significantly reduced by laser illumination of the sSC in anesthetized mice. These results indicate that photo-activation of eNpHR expressed in RGC axons enables selective blockade of retino-tectal synaptic transmission. The method established here can most likely be applied to a variety of brain regions for studying the function of individual inputs to these regions.
authors.affiliation: Department of Developmental Physiology, National Institute for Physiological Sciences, Okazaki, Japan. kkaneda@pharm.hokudai.ac.jp
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kaneda
authors.forename: Hironori
authors.initials: H
authors.lastname: Kasahara
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Matsui
authors.forename: Tomoko
authors.initials: T
authors.lastname: Katoh
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Mizukami
authors.forename: Keiya
authors.initials: K
authors.lastname: Ozawa
authors.forename: Dai
authors.initials: D
authors.lastname: Watanabe
authors.forename: Tadashi
authors.initials: T
authors.lastname: Isa
mesh_terms: D000818:Animals; D019843:Archaeal Proteins / Q000235:genetics / Q000378:metabolism; D001369:Axons / Q000378:metabolism / Q000528:radiation effects; D000229:Dependovirus / Q000235:genetics*; D015870:Gene Expression; D005822:Genetic Vectors / Q000235:genetics*; D057809:HEK293 Cells; D006216:Halobacteriaceae; D025602:Halorhodopsins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007834:Lasers; D008027:Light; D051379:Mice; D008810:Mice, Inbred C57BL; D010775:Photic Stimulation; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D013477:Superior Colliculi / Q000166:cytology / Q000378:metabolism / Q000502:physiology / Q000528:radiation effects; D009435:Synaptic Transmission / Q000528:radiation effects*; D014793:Visual Cortex / Q000166:cytology / Q000378:metabolism / Q000502:physiology* / Q000528:radiation effects*
chemical_list: D019843:Archaeal Proteins; D025602:Halorhodopsins