Jeffrey C. Magee studied both zoology and philosophy at Louisiana State University (LSU), hoping to satisfy a long-standing interest in the mind. But the trouble with philosophy, he says, is that you can't test your ideas. "It's frustrating, and that's why people don't do philosophy very much anymore," he pointed out. Neuroscience, on the other hand, "at least has a chance of giving us some insight into what makes us uniquely human. At some level, it's providing testable philosophical types of questions."
Magee chose to explore those questions as a scientist, and went on to earn a Ph.D. in physiology from Tulane University. During postdoctoral research at Baylor College of Medicine and then back at LSU, where he had returned as a professor, he made considerable contributions to the science of the mind, elucidating many of the ways in which the physical properties of nerve cells enable them to process and store information.
In 2005, after spending most of the last 25 years in Louisiana, Magee saw his lab at LSU's Health Science Center in New Orleans shut down in the wake of Hurricane Katrina. He has continued his research, but has been forced to operate out of borrowed space in a former advisor's lab in Austin, Texas. This summer, he will have a permanent lab once again—this time in Virginia, when he moves to Janelia Farm. Magee will bring two of his postdocs with him, while other lab members return to New Orleans to continue their research and help rebuild the city.
Early in his career, Magee was among the first to show that nerve cell activation relies on channels that open and shut based on fluctuations in voltage. This permits signals to enter the cell via dendrites, the branched extensions of neurons. Since then, he has worked to define how subtle changes in the properties of those channels dictate how neurons process information—a quest that he will continue at Janelia Farm. "Dendrites are loaded with different voltage-gated ion channels, and those channels produce electrical signals. Changes in those channels may change the excitability of the dendrites," explained Magee. "Similarly, differences in the ion channels in different regions of the dendrites might produce a signal that's a little bit different out in the distant part of the neuron compared to one that's closer to the cell body. These are the type of biophysical mechanisms of information processing that we're looking for."
To investigate these properties, Magee's lab studies cells in slices of adult rat brains, focusing on an area deep within the brain known as the hippocampus, which is involved in memory storage. Their studies specifically examine the activity of pyramidal cells, which store episodic memory. "We're trying to find out what sort of things these pyramidal cells are doing to enable the hippocampus to store this kind of memory—these sequences of events in our lives. We want to understand the cellular mechanisms of that memory formation," Magee said.
The outstretching surface of a neuron meets and communicates with neighboring cells at thousands of junctures called synapses. At a given time, a single neuron may receive input at hundreds of synapses, each firing up to hundreds of times per second. Like other neurons, pyramidal cells must integrate this barrage of input to glean meaningful information, which they both store as memory and use to communicate with other cells. Exactly where and when signals arrive determines how they are processed.
As he studies pyramidal cells in the laboratory, Magee wants to re-create the patterns of input they might receive in a functioning brain, examining how the timing and location of stimuli shape a neuron's response. This is challenging, because while scientists can deliver a chemical neurotransmitter to an individual neuron, the tiny size and elaborate branching patterns of its dendrites make it difficult to focus that delivery to a precise site.
Magee's group has been one of the first to overcome this challenge by employing a technique known as two-photon excitation, which biologists frequently use to see beneath the surface of living tissue. An adaptation of the technique lets Magee not only home in on a precise point on a neuron, but also confine a neurotransmitter's release to that spot. As he does so, he simultaneously records localized calcium signals and the electrical output of the cell. This allows him to study how the output changes as he stimulates the cell with different spatiotemporal patterns.
Despite the strategy's power for targeting neurotransmitter release to a defined location, Magee still has to contend with the near-impossibility of stimulating a single cell at many different locations, which is what occurs in an active brain. The available equipment simply does not move rapidly enough to release a neurotransmitter at distant locations on a single cell. In collaboration with Janelia Farm group leader Karel Svoboda and microscope designer/manufacturer Prairie Technologies, Magee is working to overcome this problem. Together, he expects they will develop new tools that will be powerful not just for his research, but also, conversely, for those who want to "zoom out" to rapidly record from or stimulate large sets of neurons.
Ultimately, Magee would like to directly investigate whether his findings about how nerve cells operate also hold true in living animals. The technology does not yet exist to carry out the same kinds of experiments in vivo, but he is optimistic that Janelia Farm is the place to speed development and make it possible. "I'm hopeful that by getting a bunch of groups together who are all interested in studying how neural networks function, and then having other people there whose primary interests are in developing new optical tools, that it will be the best place to try to move forward the kind of research we've been doing," he said.
RESEARCH ABSTRACT SUMMARY:
Jeffrey Magee is interested in how the biophysical properties of neurons produce the information-processing and storage capabilities of single and small networks of neurons.
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Photo: Tom Kleindinst