Key questions in neuroscience are: 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 will be obtained. The retina is about as complex as any other part of the brain, but it has several features that facilitate analysis: it is accessible, compact, and structurally regular, and 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 ~25 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.
A major ongoing effort is to identify recognition molecules that mediate specific connectivity in retina. To this end, we are analyzing multiple members of the immunoglobulin and cadherin superfamilies (for example, Sidekicks, Dscams, Contacts, JAMs, clustered protocadherins and Type II cadherins).
As part of this project, we are combine electrophysiological and microscopic methods to map retinal circuits in normal animals and assess alterations in mouse mutants lacking or misexpression recognition molecules.
We are also using retina as a model to analyze mechanisms underlying defects in neural structure and function that occur in normal aging and brain disorders.
Finally, we are beginning to learn how information from the retina is passed to the superior colliculus, which is the main target of retinal axons in the mouse.
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