Lab Overview

We study how circuits devoted to specific visual processing tasks arise during development of the retina, and the consequences for visual function when development goes wrong. The tools of mouse genetics are central to our approach, but we draw on a wide range of molecular, genetic, and imaging methods to tackle these questions.

Here’s what motivates our research.

Neurons differentiating to populate the embryonic mouse retina

How does the complex anatomy of a neural circuit relate to its function?

There are thousands of different cell types in the nervous system, each with its own unique and beautiful pattern of branching axons and dendrites. Other organs get by with just a handful of cell types; why does the nervous system need to be so complicated? Presumably this anatomical complexity is necessary for the brain to do its job – the encoding and transmission of information. But the relationship between anatomical structure and circuit function in the nervous system remains largely unclear.

We are trying to learn how specific neuroanatomical features enable the functions of specific neural circuits. Success in this endeavor would lead to at least three exciting new insights. First, we would gain a mechanistic understanding of how groups of neurons implement the computations that underlie sensory experience and behavior. Second, we would begin to understand why implementing these circuit functions requires so many different types of neurons, with such varied morphologies. Finally, we would identify anatomical features that make circuits vulnerable to dysfunction if they do not form properly – insights that could reveal the anatomical basis for neurodevelopmental disorders.

To investigate how neural structures enable circuit function we study the mouse retina. The retina is an ideal model system for these studies because the relationship between circuit structure and function is quite well understood; because retinal circuits are easy to access and manipulate experimentally; and because synaptic connectivity is easy to measure anatomically and physiologically. We use the tools of mouse genetics to subtly perturb circuit anatomy and make specific, testable hypotheses about the effects on circuit function. By taking advantage of all the retina has to offer as a model, we hope to pinpoint key developmental events and circuit wiring features that underlie not only visual function, but brain function more broadly.

Development as a window into the function of retinal circuitry

The dendritic arbors of a retinal cell type known as the Starburst neuron. Each cell type in the nervous system has a typical arbor shape that helps determine its function.

The crucial anatomical features that enable circuit function are established during development. Shaped by the genes they express, and their local cellular/molecular environment, developing neurons and glia grow tree-like arbors that are complex, beautiful, and stereotyped across cells of a given type. These arbor patterns determine critical circuit features such as receptive field sizes and interactions with synaptic partners.

In our lab we seek to discover the genetic and cell-biological programs responsible for establishing unique anatomical features of retinal circuits. As developmental biologists, we find these pattern-formation questions fascinating. And as neuroscientists, we see an opportunity to use development as a window into circuit function: Once we know the mechanisms responsible for formation of a specific anatomical feature, we can perturb those mechanisms to change anatomy in subtle but defined ways. These changes allow us to ask whether and how specific anatomical features contribute to information processing by retinal circuits.

Over time, as we build a large library of developmental mutants that change circuit anatomy, this approach will reveal larger patterns: What types of anatomical features are always needed for circuit function? What features are dispensable or subject to compensation that preserves function when they do not develop properly? Insight into these questions will advance our knowledge of how retinal circuit computations are enabled by their function. Moreover, this approach has the potential to reveal general principles that define how developmental changes produce circuit dysfunction, with implications for understanding the anatomical basis of developmental disorders.