Abstract
Bipolar cells relay visual signals from photoreceptors to ganglion cells. In the mouse retina, fifteen bipolar cell subtypes have been identified and are classified as ON or OFF bipolar cells based on their responses to light, or as rod or cone bipolar cells based on their photoreceptor connectivity. Despite this diversity, the distinct structural and functional roles of bipolar cell subtypes in visual information processing remain poorly understood, largely due to lack of tools and models for their characterization. In this study, we generated inducible Cre mouse lines driven by the promoters of Vsx1, Lhx3, and Lhx4 and crossed them with ChR2EYFP reporter mice to trace lineage and characterize bipolar cell subtypes in postnatal and adult mouse retinas. Following tamoxifen induction in adult male and female mice, ChR2EYFP expression was detected in type 2, 6, and 7 bipolar cells in the Vsx1CreERT2 line, type 1b, 2, and 6 bipolar cells in the Lhx3CreERT2 line, and type 2, 3, 4, and 5 bipolar cells in the Lhx4CreERT2 line. In addition, Lhx4CreERT2 activity was observed in cone photoreceptor cells. ChR2EYFP expression was also detected in other ON and OFF cone bipolar cells, as well as rod bipolar cells, when tamoxifen induction was performed in the postnatal mice. These inducible Cre lines enable genetic manipulation in retinal bipolar cell subtypes at different developmental time points, and serve as tools for elucidation of the mechanisms that control bipolar cell subtype development and function.
Significance Statement Bipolar cells are central connectors of the outer and inner retina and initiate processing of complex visual information. Bipolar cells differentiate into more than fifteen subtypes during development, and their structural diversity has been well studied. However, the unique contribution of these subtypes to visual information processing is poorly understood due to inadequate tools. In this study, we develop and characterize three inducible Cre mouse models for temporally-defined genetic manipulation in bipolar cell subtypes in the developing and adult mouse retina. These models serve as tools to elucidate the mechanisms that regulate development and function of bipolar cell subtypes in the mouse retina.
Footnotes
Authors would like to thank the Augusta University Imaging Core for their support
Authors report no conflict of interest
The research was funded by National Eye Institute grant (EY026614) to LG and by National Eye Institute P30 Core grant P30EY031631 at Augusta University
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
