The full moon is about a million times brighter than the dimmest star the eye can detect. Yet we can see both if we're far enough away from city lights. This impressive dynamic range and other astounding features of vision are why Gabe Murphy is awed by the eye. It's also why he spends entire days in a dark lab learning how the electrical signals that light evokes propagate through the retina's neural circuits. "With the retina, the input [light] is very clear, and the output [nerve impulses] can be measured very precisely," he says. "And the output is very important, because it is the entire basis for our visual perception."
Murphy wanted to become a doctor after watching procedures in the operating room and seeing how much satisfaction his grandfather derived from being an anesthesiologist. But after spending a couple of summers in a Stanford lab, he realized how much fun research could be. "One of the nice things about science is that it is very deliberative," he says. "In the operating room, things happen very quickly. But as a scientist, I can sit down and think really hard about something for however long it takes."
Murphy's experiments take place in a dark room, where he delivers precisely calibrated light stimuli and records the electrical impulses they elicit in a variety of retinal neurons. This system is appealing, he explains, because the retina responds to light as if it were still in the eye. "This complex system has lots of neat properties that we would like to understand," he says. "But it is sufficiently simple and tractable that we can go in there and do lots of precise biophysical measurements that might be difficult to do in vivo."
He first studied the retina as a graduate student, when he spent a summer at the Marine Biological Laboratory in Woods Hole, Massachusetts, courtesy of a Grass Fellowship. In 14 weeks, he carried out a project entirely by himself for the first time. "I really valued my relationship with my graduate adviser," he says. "But going to Woods Hole helped me feel confident that I could come up with a neat idea completely of my own design, see that idea through, and analyze the data on my own."
This realization and the desire to identify the contributions of specific biophysical processes to the patterns of neural activity elicited by sensory stimuli led him to the University of Washington to begin postdoctoral studies in 2004 with Fred Rieke (who became an HHMI investigator the following year). The question he began to ask is how a signal is changed as it passes through the retina and how that transformation affects the image we see.
In the retina, photoreceptor cells (rods and cones) receive light signals, which they transform into coded electrical signals, as a TV camera does. This information is sent to other neurons and then to the retina's ganglion cells, which, in turn, send signals to the image-processing parts of the brain. But the signals sent from the ganglion cells vary, even if the amount of light received by the photoreceptor cells is the same.
Scientists had long debated about the extent to which variability in the output of neurons recorded in vivo was due to "noise" in the neuron itself or to noise in the inputs the neuron receives. "Because we can precisely control the input and measure the output, we showed pretty directly that almost all of the variability in the output from the ganglion cells reflects variability in the input the ganglion cells receive," Murphy says.
Understanding the mechanisms that transform light-evoked signals in the healthy retina will be a valuable step toward developing solutions to diseases that affect retinal processing. Retinal prostheses have begun to show promise in clinical trials, but scientists will need to better understand how the retina transforms sensory information before those devices can provide precise information about the visual world. "[Building such prostheses] is an exciting possibility," Murphy says, "albeit one that is many years away."
He says that one of the most challenging, but also enjoyable, aspects of his research is the need to understand physics, optics, electronics, behavior, and chemistry. "It is a huge draw of what I do, but also something that keeps me up late at night," he says. "Sometimes I worry that I can't grasp everything I'd like."
The move to Janelia Farm has been helpful, he adds, because researchers there are designing innovative equipment and techniques that can be applied to biological questions. He is particularly excited by the unique combination of investigators focused on advanced microscopy, biophysical properties of neural circuits, and those circuits' contributions to behavior. "Those are the three big things I am working on," he says. "And to have the resources all in the same place is a remarkable opportunity."
RESEARCH ABSTRACT SUMMARY:
Gabe Murphy explores properties of synapses, cells, and circuits that underlie the specificity and fidelity with which the nervous system encodes information about sensory stimuli.
View Research Abstract
Photo: Paul Fetters