Cell and Neurobiology
Zilkha Neurogenetic Institute
Keck School of Medicine of USC
Research TopicsSystem Neuroscience Neural Population Coding Neural Circuits Retinal Neurophysiology
Research OverviewThe brain is comprised of many complex circuits. Each circuit processes specific kinds of information such as visual images, music, language, or controlling muscles. These neural circuits are difficult to study because they consist of hundreds, thousands, or even tens of thousands of neurons, and they display complex and specific connectivity patterns. How are we to understand these circuits, or the meaning of a signal carried by a particular neuron within a circuit, if we do not understand how neurons are wired together and how they function in concert? Thus, a major obstacle limiting our understanding of neural circuits is a lack of techniques for mapping the functional connectivity among neurons, the building blocks of the brain.
To understand how neurons function within circuits, my lab uses large-scale multi-electrode arrays to record the activity of hundreds of neurons simultaneously. We combine this with optical stimulation of other neurons within the circuit to map how the activation of one neuron influences the activity of another neuron, and to map the functional connectivity among thousands of neurons within the circuit. We use the mammalian retina as our model neural circuit for several reasons. First, it is relatively natural to study the retina in isolation because it does not receive feedback from the rest of the brain. Second, the photoreceptors (light sensitivity neurons in the retina) can be precisely stimulated by their natural input, light. Third, the retina exhibits a rich diversity of ~80 distinct cell types, each with its own specific set of connections within the retina. Fourth, retinal degenerative diseases are a leading cause of blindness, thus understanding how the retina functions in health and disease will be key to developing promising therapies for restoring vision (e.g. retinal prosthetics, drug discovery, or stem cells).
Current research questions in my lab are centered around identifying the functional connectivity between the photoreceptors (both rods and cones) and the ~20 distinct retinal ganglion cell types. The retinal ganglion cells are the ?output? cells of the retina, sending information to the brain. What are the rules that govern this connectivity? Do these rules differ between cell types? How does this functional connectivity change as the retina adapts to different visual environments? We are also developing techniques for mapping the connectivity among retinal interneurons to reveal how these specialized cells within the retina communicate information from the photoreceptors to the ganglion cells. Finally, we are investigating how stem-cell based therapies can be used to reverse the effects of retinal degeneration.