Abstract
Purpose :
Rods evolved from cones; rod and cone bipolar cells must therefore have been initially similar, with ON and OFF cells synapsing directly onto ganglion cells. In mammals and teleost fishes, however, there are no OFF rod bipolar cells (RBCs), and ON RBCs synapse onto AII amacrine cells, which then convey the rod signals to cone bipolar cells and thence to ganglion cells. We attempt to explain how and when this transformation occurred.
Methods :
Single-cell RNA sequencing (scRNA-seq) was used to characterize retinal cell types in lamprey and to compare them to cell types in higher vertebrates (chicken, mouse, and macaque). Recordings from lamprey bipolar cells were made using patch-clamp in retinal slices.
Results :
scRNA-seq analysis of the adult lamprey retina obtained over 20,000 high-quality single-cell transcriptomes. An unsupervised clustering method was used to cluster all the cells into six main classes, as in all other vertebrates. From the BC class, there are three subclasses, RBCs, ON BCs, and OFF BCs, identified based on the expression patterns of canonical markers and synaptic receptor genes. The RBCs were further divided into two ON RBCs and one OFF RBC. One amacrine type had clear affinities to mammalian AII amacrines but did not express gap junctions. Single-cell recordings from lamprey retina identified an OFF RBC with spectral sensitivity nearly indistinguishable from rods. In backgrounds known to saturate rods, OFF RBCs were also saturated and did not respond to increment flashes.
Conclusions :
When cyclostomes split off from other vertebrates over 500 mya, lamprey progenitors had both ON and OFF rod bipolar cells and AII-like amacrine cells which did not however function like AII amacrines in mammals. Both rod and cone signals would have been processed in a similar fashion by direct input to ganglion cells. Since salamander and mudpuppy also have OFF RBCs, we think the processing of rod signals continued to occur via direct synapses onto ganglion cells up to the time of the split of amphibians from other vertebrates about 400 mya. At least some amphibians retained both ON and OFF RBCs, but OFF RBCs were gradually and independently lost in teleost fishes and mammals. AII-amacrine cells are very old but only later in evolution developed connections to rod and cone bipolar cells, forming the circuits that eventually replaced the more ancient system of direct synaptic contacts from both rod and cone bipolar cells to ganglion cells.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.