Cell-type-specific Cre driver lines have revolutionized the analysis of retinal cell types and circuits. We show that the transgenic mouse Rbp4-Cre selectively labels several retinal neuronal types relevant to the encoding of absolute light intensity (irradiance) and visual motion. In the ganglion cell layer, most marked cells are wide-field spiking polyaxonal amacrine cells (ACs) with sustained irradiance-encoding ON responses that persist during chemical synaptic blockade. Their arbors spread about a millimeter across the retina and are restricted to the inner half of the ON sublamina of the inner plexiform layer. There, they costratify with dendrites of M2 intrinsically photosensitive retinal ganglion cells (ipRGCs), to which they are tracer-coupled. We propose that synaptically-driven and intrinsic photocurrents of M2 cells pass through gap junctions to drive AC light responses. Also marked in this mouse are two types of retinal ganglion cells (RGCs). ‘R-cells’ have a bistratified dendritic arbor, weak directional tuning, and irradiance-encoding ON responses. However, they also receive excitatory OFF input, revealed during ON-channel blockade. Serial blockface electron microscopic (SBEM) reconstruction confirms OFF bipolar input, and reveals that some OFF input derives from a novel type of OFF bipolar cell. R-cells innervate specific layers of the dorsal lateral geniculate nucleus and superior colliculus. The other marked RGC type (‘RDS’) is bistratified, transient, and ON-OFF direction-selective. It apparently innervates the nucleus of the optic tract. The Rbp4-Cre mouse will be valuable for targeting these cell types for further study and for selectively manipulating them for circuit analysis.
Significance Statement Genetically modified Cre strains permit cell-type-specific labeling and functional manipulations. We illustrate the utility of Rbp4-Cre mice for studying selected retinal cell types that encode the intensity of light and the direction of motion. Intensity encoding is thought to be uniquely mediated by intrinsically photosensitive retinal ganglion cells (ipRGCs). ipRGCs transmit intensity signals not only to the brain, but also intraretinally, partly through gap junctions to polyaxonal amacrine cells. We show that these amacrine cells are tagged in Rbp4-Cre mice, confirm their persistent light responses under chemical synaptic blockade, and show that they co-stratify with, and are tracer-coupled to M2 ipRGCs. The line also labels a variant of direction-selective RGCs, and a RGC that lacks intrinsic photosensitivity but encodes intensity.
- amacrine Cells
- Bipolar Cells
- Direction-Selective Ganglion Cells
- Intrinsically Photosensitive Retinal Ganglion Cells
1 Authors report no conflict of interest.
3 This project was supported by the Banting Postdoctoral Fellowship of Canada to S.S., The Sidney A. Fox and Dorothea Doctors Fox Postdoctoral Fellowship in Ophthalmology and Visual Sciences to S.S., and NIH grant (R01 EY12793) and an award from the Alcon Research Institute to D.M.B.