The tiny, twitching nose of a mouse can detect and discriminate between countless different odors. As the odors emanating from a tasty snack of grains or a potential mate reach the neurons in the mouse's nose, olfactory information is relayed to the brain, where an elaborate chemical code is deciphered. To Dmitry "Dima" Rinberg, however, the detection of that vast array of odors is merely the first step in a process that has much to reveal about how the brain works.
Rinberg believes behavior is the key to deciphering the signals that fly like instant messages between the nose and the brain, enabling mice to put olfactory information to use. "When a mouse sniffs, it is not just sensing an odor," Rinberg said. "It is making behavioral decisions based on that odor." As an example, he cites an experiment he uses in his lab in which thirsty mice quickly learn where to turn for water when the location is linked to a particular scent—turning to the right when they smell mint and to the left when the clue is a whiff of almonds.
Rinberg has proposed a new framework for studying sensory processing that centers around behaving animals—an approach he will bring to Janelia Farm along with his trained mice, miniaturized neuronal recording equipment, and questions about the olfactory system. There, he plans to draw on the genetic, optical imaging, and data processing expertise of his new colleagues "to decode the olfactory code in behaving mice by all possible means," he said.
Much of what is known about the mouse's olfactory system comes from anesthetized unconscious animals, in part because of the technical challenge of recording neuronal activity in small, active animals. To address these difficulties, Rinberg spent two years developing a miniature device to record the electrical activity of several nerve cells at once in the olfactory bulbs in the brains of mobile mice. The device, which fits directly onto a mouse's head, allows an experimenter to record the activity of several neurons, switching between them as easily as tuning into different radio stations. To bring this technology to more researchers, Rinberg founded a company called RP Metrix (which he left when he came to Janelia Farm) to produce similar devices.
Rinberg's first experiments in his mouse model confirmed a dramatic difference in the nerve activity in the olfactory bulb of an awake mouse and the same mouse when anesthetized. He recorded mitral cells, which receive signals from olfactory receptors in the nose and relay the information to higher brain areas. Different mitral cells respond to different odors. In anesthetized animals, the background mitral cell activity was low, and odors caused a noticeable jump in signaling. In awake animals, on the other hand, the same cells maintained a much higher level of background activity. In the single-cell recordings, odors made a barely perceptible blip in neuron firing, even those that produced obvious behavior changes in the trained mice.
It may be that the crucial circuits lie in only a few mitral cells, and Rinberg missed them in his recording. Or it may be that many neurons work together in a kind of synchrony that individual neuron recording cannot detect. At Janelia, he hopes to be able to record many more neurons simultaneously with a new optical recording technique. "We need to study neurons at every level—how they talk to each other, grow, and create networks, but the final goal is to understand how these small blocks build behavior," he said.
Rinberg traveled a circuitous intellectual and geographic route to Janelia. As an undergraduate in Moscow, he studied material physics and stayed on as a junior researcher in low-temperature physics. Then, he and his family emigrated to Israel where his doctoral studies in low-temperature fluid dynamics opened up the broader world of physics to him. He saw a great opportunity to apply his training to biology.
He came to this country as a postdoctoral fellow, first working on sensory information processing in the cockroach. He proposed a mechanism that may explain how cockroaches distinguish between threats like a frog or a rolled up newspaper and a harmless breeze coming through a window.
Rinberg continued his postdoctoral training at Lucent's Bell Labs in New Jersey and moved with neuroscientist Alan Gelperin to Monell Chemical Senses Center in Philadelphia as a research associate, where he trained mice and miniaturized electrophysiology recording devices.
Also during his work at Monell, he and colleagues at the University of California, San Diego, patented a new shotgun to fire gene-covered microbeads into neurons. The original technique was invented more than 20 years ago to penetrate the tough hides of plant cells, but the accompanying air pressure damages the more delicate neuronal tissues. Rinberg found a way to eliminate the damaging air pulse shock wave.
Rinberg expects life at Janelia to contrast dramatically with what he might experience at a university, where he said he would likely spend 80 percent of his time writing grants and managing the lab. He thinks Janelia Farm will be a better match for his personality, since he is eager to spend time both working in the lab and engaging in discussion with colleagues who share a common interest, but approach their research with very different perspectives and expertise. Since other Janelia researchers are equally eager to collaborate and consult with one another, Rinberg says the campus will have the "brainstorming atmosphere" that he's looking for.
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