How are complex neural circuits assembled in young animals? And how do they process information in adults? The retina may be the first part of the mammalian brain for which satisfactory answers to these questions can be obtained.
The Sanes lab therefore studies the assembly and function of neural circuits in the retina. While the retina is about as complex as any other part of the brain, it has several features that facilitate analysis. Additionally, we already know a lot about what it does.
Visual information is passed from retinal photoreceptors to interneurons to retinal ganglion cells (RGCs) and then on to the rest of the brain. Each of >40 types of RGC responds to a visual feature –for example, motion in a particular direction– based on which of the >70 interneuronal types synapse on it. To understand how these circuits form, we mark retinal cell types transgenically, map their connections, seek recognition molecules that mediate their connectivity, use genetic methods to manipulate these molecules, and assess the structural and functional consequences of removing or swapping them. We believe that our methods and results will be useful in tackling less accessible parts of the brain such as the cerebral cortex.
We are also using the retina to address the thorny problem of neuronal classification, which is a bottleneck for neuroscience generally. We use high-throughput single cell RNA sequencing to profile tens of thousands of retinal cells, then apply bioinformatics methods to categorize them. We are now beginning to use the mouse “retinone” as a foundation for analyzing gene expression in mouse models of human blinding diseases, and for classifying neurons in the primate retina, which differs in important ways from that of the mouse.