Roska explaining the cell layers of the retina. Robert Sanders photo

Though scientists realize that the eye is not merely a camera providing digital input to the brain, the general consensus has been that the world projected onto the retina and detected by cells called photoreceptors got sent to the brain after some relatively simple processing.

Roska and Werblin showed that retinal cells do a lot of processing to extract only the essence of the picture to send to the brain. The anatomy of the retina is layered to facilitate this.

Light initially impinges on the light-sensitive cells of the eye, the photoreceptors, which fire off signals to a layer of horizontal cells and thence to bipolar cells. Since 1969, Werblin has been recording from all retinal cells and has detailed how each cell type processes data from the photoreceptors.

The bipolar cells funnel signals down their axons — the outgoing wires of the nerve cell — and relay them to the dendrites or input wires of ganglion cells, which send the processed information to the brain. All these cell types are arrayed in unique layers, stacked one atop the other.

Light excites the photoreceptors (top), which relay signals through the horizontal cells (green) to the bipolar cells, which in turn send signals through the various layers of dendrites to the ganglion cells (bottom). The ganglion cells bundle together into the optic nerve and carry the output of the eye to the brain. See video page for detailed explanation. Frank Werblin image

Biologists noted earlier that all ganglion cells were not alike and that they fired off different information to the brain, though the details were hazy. Part of the reason is that the axons from the bipolar cells synapse with or touch the dendrites of the ganglion cells in a tangled region (the inner plexiform layer) that made biologists despair of making sense of the connections.

Roska discovered, however, that this region of tangled axons and dendrites is really laid out in orderly strata. By staining the cells from which he recorded, he found that bipolar cell axons converge on 12 or so well-defined layers, where they synapse with the dendrites of the ganglion cells. Each layer of dendrites belongs to a specific population of ganglion cells.

Without interaction between layers, though, the signal emerging from the tangle would not be much different from the original 12-channel output of the bipolar cells. The critical element is another type of cell, the amacrine cells, which send processes to the various layers of dendrites and allow the layers to talk with one another. This cross-talk is what allows the layers to process the visual data and extract the sparse information that the ganglion cells send up to the brain.

"These layers actually converse with each other, they make comparisons and subtractions and differences," Werblin said. "They say, what is the essential feature here. Then they send out these 12 or so moving pictures to the brain.

Roska's experimental technique allowed him not only to measure the output of ganglion cells, but the excitations they received from bipolar cells and the inhibitions they received from amacrine cells. With this information he is now reconstructing the conversations between layers that result in the final output going to the brain.

"Any one layer is being read out by, let's say, a hundred thousand cells, each with its own axon sending information to the brain. There's another layer reading out another hundred thousand. And all of those combine in the full optic nerve, which is carrying maybe a dozen different masses of fibers," Werblin explained. "Eventually many of these movies get to the visual cortex, the entry to whatever we use to generate consciousness."

Though Roska is returning to Hungary for a year, he will continue his experiments there on the amacrine cells.

"The fundamental question now is, why do certain layer talk to one another," said Roska, who a year from now will embark on a prestigious three-year fellowship at Harvard University as a junior fellow of the Society of Fellows

"Previously, when people studied ganglion cells, they would look at the cell and flash lights. One of Botond's major contributions to this was, he thought about this not as the cell, but as the layer of processes from which the cell is reading. So, we began to think in terms of layers, and all of the activity we measured corresponded to what happened in a particular layer," Werblin explained. "Then it became clear that these layers were actually talking to each other. Previously no one had even thought that these layers talked to one another, even though 100 years ago the picture was there. No one had really looked at that picture."

The work was supported by grants from the Office of Naval Research and the National Institutes of Health.