Medicine on the Midway - Spring 2016

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Wei Wei, PhD, was recently selected for a 2016 McKnight Scholar Award from The McKnight Endowment Fund for Neuroscience to support her research on dendritic processing of visual motion in the retina.

into multiple streams of information long before any signals reach the brain.” Whether it travels light years from the stars or nanoseconds from a light bulb, every photon we see ends its journey at the retina, a thin layer of tissue in the back of the eye and the only visible part of the brain. Networks of neurons here calculate information about motion, color, direction, light intensity and more, while ignoring irrelevant features. The combination of around 20 to 40 different types of these neural circuits, each responding very differently to the same photons, is what the brain ultimately uses to construct vision. As the rodent retina under the microscope in her lab performs its computations, Wei and her team


“The retina is more like a little computer that starts processing visual inputs into multiple streams of information long before any signal reaches the brain.” Wei Wei, PhD


are most interested in the activity of one particular cell class, the retinal ganglion cell. These are the only neurons directly wired to the rest of the brain, and the signals they send down the optic nerve depend entirely on what they “see.” In this case, the researchers are focused on ganglion cells that respond only to specific directions of motion. As the projector shines an image of a tiny black bar moving from left to right on their receptive field, these cells fire enthusiastically. When the bar moves from right to left, they remain silent. This selectivity is possible because each ganglion cell receives signals from dozens of intermediary neurons, which in turn are processing the spatial and timing activity of 100 or more photoreceptors. Like resistors or conductors in an electrical circuit, intermediary neurons organize the flow of information by increasing or decreasing the activity of other neurons in their network. Their combined effect is how a ganglion cell “sees” motion. Wei wants to understand and reverse engineer this circuit. To do so, she breaks parts of it. Leveraging


a powerful combination of molecular, genetic and imaging techniques, her lab can manipulate its activity in extremely precise ways. For this experiment, her team uses a genetic “switch” to turn off only synapses that transmit an activity-decreasing signal. They then ask: If the ganglion cell doesn’t receive this information, will it still be selective to direction? The grossly oversimplified answer is, surprisingly, yes. Contrary to assumptions, these neurons retain a great deal of their direction selectivity even in the absence of half the input they normally receive. “Our work has shown that there must be multiple neural mechanisms that interact synergistically to ensure robust detection of motion, and are used together to foolproof the system,” said Wei, who published the results of this study in the Journal of Neuroscience last fall. “If you disrupt any one particular mechanism, even one we thought was absolutely critical, there are others that can compute motion direction, albeit suboptimally.” Investigating the brain’s higher functions Many more studies are needed to answer the numerous questions that Wei’s findings raise, not least of which is how these circuits continue to compute. But the implications impact much more than just vision. Regardless of location or function, neural circuits work in largely the same way: They receive some input, send signals to increase or decrease each other’s activity and collectively generate an output. Multiple mechanisms built into this process could perhaps be one of the reasons why the brain can be so dependably relied upon to carry out all its complex functions. “We have this amazing ability to think, to reason, to make sense of things in our environment,” said David Freedman, PhD, associate professor in the Department of Neurobiology. “The brain is able to take in sensory information and produce meaningful experiences and behavior. We think there is a general set of rules for how this information flows through the brain, and identifying these rules at the circuit level is one of the greatest challenges in science.” Whatever the stereotype of a neuroscientist might be, it’s unlikely that Freedman fits it. When he moonlights with his funk and soul-jazz band (co-founded by fellow UChicago neuroscientist Sliman Bensmaia, PhD) at various bars and venues across Chicago, probably few in the audience would guess that the lead guitarist with the dark blond locks is also chair of a computational neuroscience graduate program. For Freedman, the visual system is a window to our higher cognitive functions. His research focuses on a particular phenomenon known as