A Cre Mouse Line for Probing Irradiance- and Direction-Encoding Retinal Networks

Abstract

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 (GCL), 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 1 mm across the retina and are restricted to the inner half of the ON sublamina of the inner plexiform layer (IPL). 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 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 (BC). R-cells innervate specific layers of the dorsal lateral geniculate nucleus (dLGN) and superior colliculus (SC). The other marked RGC type (RDS) is bistratified, transient, and ON-OFF direction selective (DS). It apparently innervates the nucleus of the optic tract (NOT). The Rbp4-Cre mouse will be valuable for targeting these cell types for further study and for selectively manipulating them for circuit analysis.

Genetic access to neurons in the accessory optic system reveals a role for Sema6A in midbrain circuitry mediating motion perception

“…Retinal ganglion cells can be classified into ~30 subtypes distinguished by visual response properties, morphology, synaptic connectivity, gene expression profiles and response to optic nerve injury (Duan et al, ; Sanes & Masland, ). The visual response properties encoded by retinal ganglion cells include intrinsic photosensitivity, color opponency, contrast sensitivity, looming object detection, and direction selectivity (Duan, Krishnaswamy, la Huerta, & Sanes, ; Ecker et al, ; Huberman et al, ; Joesch & Meister, ; K. P. Johnson, Zhao, & Kerschensteiner, ; Kim, Zhang, Yamagata, Meister, & Sanes, ; Krishnaswamy, Yamagata, Duan, Hong, & Sanes, ; Sabbah, Berg, Papendorp, Briggman, & Berson, ; Y. Zhang, Kim, Sanes, & Meister, ). Directionally selective retinal ganglion cells (DS RGCs) increase their firing rate when movement in a preferred direction occurs within their receptive fields (Mauss, Vlasits, Borst, & Feller, ).…”

Synaptic circuits for irradiance coding by intrinsically photosensitive retinal ganglion cells

“…Extended Data Figure 2 shows all reconstructed BCs per type, along with their stratification patterns and mosaics. In addition to the 13 known cone BC types and a single rod BC type 11,29 , we identified another cone BC type -Type 0 30 . Figure 1a-c shows representatives examples of each BC type and group data on their terminal field area and IPL stratification depth.…”

“…Whole-cell patch-clamp current-clamp and voltage-clamp recordings of isolated flat-mount retinas were performed as described 48…”

“…Acquired time-series images were registered, and dendritic glutamate responses were analyzed using FluoAnalyzer 22 and custom Matlab scripts 48 . We employed two distinct approaches.…”

“…This intraretinal dopaminergic signaling, in turn, modulates chemical and electrical synapses and modifies the functional properties of retinal neurons, thereby modulating the dynamic range over which the retina operates41 . Additionally, ipRGCs have been recently shown to inject their intensity signals by means of electrical transmission through gap junctions to a family of spiking polyaxonal amacrine cells whose somata are unconventionally placed in the ganglion cell layer30,42 . However, it is unclear whether these intensity signals are transmitted within the retina or modulate its sensitivity.Supplementary Information is available in the online version of the paper.…”