Information processing in the brain occurs at synapses, and defects in synapse formation are likely to underlie many neurological and psychiatric diseases. We are therefore interested in the molecules and structures that regulate synapse formation, with a particular emphasis on its specificity: how axons choose appropriate partners from among dozens to hundreds of potential targets to form the complex circuits that underlie mental activities. It is now clear that the selection relies on molecular recognition between partners, forming rudimentary patterns of connectivity that may then be refined by experience.

We have chosen to study this remarkable recognition process in the visual system. In particular, we ask how the cells that connect the retina to the brain receive appropriate synapses on their dendrites in the brain and seek out appropriate targets with their axons. The retina is about as complex as other parts of the brain, but has several technical advantages that enable detailed analysis. Our studies rely heavily on genetically engineered mice, both to mark cells so we can image their development and pattens of connectivity, and to manipulate cells so we can test candidate recognition molecules. We also test the functions of the circuits formed.

More recently, we have used molecular methods to confront the complexity of the retina. By profiling gene expression in tens of thousands of single retinal cells, we are able to classify them into types and characterize their complements of recognition molecules. We have found that the retinas of mice and humans contain approximately 130 and 80 cell types, respectively. We are now using these methods to learn how the retina develops and responds to injury. We are also generating cell atlases from retinas of numerous vertebrate species to address issues of brain evolution.