title: Targeted Expression of Channelrhodopsin-2 to the Axon Initial Segment Alters the Temporal Firing Properties of Retinal Ganglion Cells.
abstract: The axon initial segment (AIS) is essential for initiating action potentials and maintaining neuronal excitability in axon-bearing neurons in the CNS. There is increasing interest in the targeting of optogenetic tools to subcellular compartments, including the AIS, to gain precise control of neuronal activity for basic research and clinical applications. In particular, targeted expression of optogenetic tools in retinal ganglion cells (RGCs) has been explored as an approach for restoring vision after photoreceptor degeneration. Thus, understanding the effects of such targeting on spiking abilities and/or patterns is important. Here, we examined the effects of recombinant adeno-associated virus (rAAV)-mediated targeted expression of channelrhodopsin-2 (ChR2)-GFP with a NaV channel motif in mouse RGCs. We found that this targeted expression disrupted NaV channel clustering at the AIS and converted the spike firing patterns of RGCs from sustained to transient. Our results suggest that the clustering of membrane channels, including NaV channels, at the AIS is important for the ability of RGCs to generate sustained spike firing. Additionally, the targeting of optogenetic tools to the AIS with the NaV channel motif may offer a way to create transient light responses in RGCs for vision restoration.
authors.affiliation: Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States of America.
authors.forename: Zhifei
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States of America.|Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States of America.
authors.forename: Chaowen
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States of America.
authors.forename: Qi
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States of America.|Department of Ophthalmology, Kresge Eye Institute, Wayne State University School of Medicine, Detroit, Michigan, United States of America.
authors.forename: Zhuo-Hua
authors.initials: ZH
authors.lastname: Pan
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000378:metabolism*; D000075402:Channelrhodopsins; D000229:Dependovirus / Q000235:genetics*; D007124:Immunoenzyme Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism*; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism*
chemical_list: D000075402:Channelrhodopsins; D061566:Voltage-Gated Sodium Channels