Type 3a and type 3b OFF cone bipolar cells provide for the alternative rod pathway in the mouse retina

The mammalian retina provides several pathways to relay the information from the photoreceptors to the ganglion cells. Cones feed into ON and OFF cone bipolar cells that excite ON and OFF ganglion cells, respectively. In the "classical" rod pathway, rods feed into rod bipolar cells that provide input to both the ON and the OFF pathway via AII amacrine cells. Recent evidence suggests an alternative rod pathway in which rods directly contact some types of OFF cone bipolar cells. The mouse has become an important model system for retinal research. We performed an immunohistochemical analysis on the level of light and electron microscopy to identify the bipolar cells and ganglion cells that are involved in the alternative rod pathway of the mouse retina. 1) We identify a new bipolar cell type, showing that type 3 OFF cone bipolar cells comprise two distinct cell types, that we termed 3a and 3b. Type 3a cells express the ion channel HCN4. Type 3b bipolar cells represent a hitherto unknown cell type that can be identified with antibodies against the regulatory subunit RIIbeta of protein kinase A. 2) We show that both 3a and 3b cells form flat contacts at cone pedicles and rod spherules. 3) Finally, we identify an OFF ganglion cell type whose dendrites costratify with type 3a and 3b bipolar cell axon terminals. These newly identified cell types represent the basis of a neuronal circuit in the mammalian retina that could provide for an alternative fast rod pathway.