In an effort to further understand the mechanisms of vision and to predict the outcomes of visual diseases, a team of scientists studied the circuitry of retinal ganglion cells of mice. The work, published recently in Neuron, comes from a collaboration between the Friedrich Miescher Institute (FMI), the Institute of Molecular and Clinical Ophthalmology Basel (IOB), ETH Zurich, and the Ecole Normale Supérieure.
The team developed a method to control the activity of horizontal cells—an interneuron type that provides feedback at the first visual synapse. The method, which involved a specific set of viruses, transgenic mice, and engineered ligand-gated ion channels, allowed the team to switch the feedback on and off.
To measure the effects of this perturbation in the retinal output, the team used high-density microelectrode arrays and recorded the electrical signals of hundreds of ganglion cells simultaneously. Surprisingly, the perturbation caused a large set of different changes in the output of the retina. After measuring the signals in thousands of ganglion cells and in defined retinal output channels, it became clear that the variety in the horizontal cell contributions arose from the specific architecture of the retinal circuitry.
To account for these effects, the team built a computer model of the retina. The model simulated the different pathways that the signal can take through the retina, and enabled the team to investigate if our current understanding of the retinal circuitry could account for the effects they observed during the experiments. It became apparent that the model could reproduce the entire set of changes that were first measured experimentally. In addition, the team found that the model made five further predictions about the role of horizontal cells, which they had previously not seen in the data.
“One way to test our understanding of the retina is to perturb one of its elements, measure all the outputs, and see if our ‘understanding’, which is a model, can predict the observed changes,” explains study senior co-author Rava A. da Silveira.
“The next step is to use the model to predict the outcome of eye diseases,” adds another co-author, Botond Roska.
See the full news release from IOB.