Campus & Community

Lichtman probes battle of nerves

5 min read

Color-coded nerves show way

Jeff Lichtman challenges conventional wisdom about nerve production: ‘The nervous system could be built perfectly from the get-go, as perhaps it is in some lower animals. The mammalian nervous system, however, allows an intelligent choice of what to maintain and what to get rid of.’ (Staff photo Kris Snibbe/Harvard News Office)

There’s a war going on inside our bodies, early in life.

The combatants are motor nerve cells, the strangely branched bodies that carry nerve signals from our brains to our muscles and that are responsible for all our movements, from a sprint across a field to the tiniest twitch of a finger.

The prize is the muscle fibers they are struggling to control. Each nerve cell sends out multiply-branched fingers called axons that contact many muscle fibers, which are also in contact with axons from other nerve cells.

And a battle ensues.

The different nerve endings compete back and forth until one is the victor and becomes the conduit for messages from the brain to that particular bit of muscle.

In the meantime, the battle leaves us pretty helpless.

That, according to new Professor of Molecular and Cellular Biology Jeff Lichtman, is the real reason human babies start out as needy as they do in life.

“A baby can’t turn over, can’t understand language, its coordination is lousy, it can’t see very well,” Lichtman said. “There’s something not right about every aspect of their nervous system.”

Conventional wisdom was that a baby’s helplessness was due simply to a lack of nerve endings in the developing nervous system, and that coordination developed as the nerves did, reaching out and forming synapses, ensuring a clear path for signals from the brain to the muscle.

But Lichtman’s results suggest the opposite is true. Instead of having too few nervous connections, babies have too many. Early on, each bit of muscle is in contact with many nerve cells, resulting in overlapping connections and a weak, confused signal. Similar overlapping connections may be present in other parts of the developing nervous system.

Lichtman’s research has focused on the competition between nerves and how the body sorts out this early confusion. He and his colleagues have worked out ways to actually watch what happens when two nerves try to connect to the same muscle.

“We see that one takes over territory and the other slinks away,” Lichtman said. “We’ve been studying the slinking, what happens when an axon goes away.”

Surprisingly, Lichtman said, the competition is not very straightforward. Rather than one nerve cell getting the upper hand and maintaining it, the battle waxes and wanes until there is a victor.

“The competition itself is much more interesting than we imagined,” Lichtman said. “We found you could not predict which would win until the competition was over.”

The key to understanding the competition between two nerves over a single muscle fiber is to know that with its many branches, that nerve cell is also competing elsewhere. Lichtman said it eventually became clear that the fewer branches a nerve cell had, the more successful it was in competition.

“The neuron that had less to do always won out,” Lichtman said.

The result of all this strife is a system that slowly eliminates connections between nerves and muscles to leave behind a web of the strongest, most reliable connections.

“The purpose of neurons is to consistently drive muscle fibers to contract. If a neuron has too much to do, maybe it won’t be able to do it efficiently,” Lichtman said. “In the end, every neuron strongly activates a subset of the target cells it initially connected with in a reliable way.”

The system fits nicely with our big brains and our ability to learn from experience, Lichtman said. Rather than being born hardwired to do certain things, such as occurs with an insect’s nervous system, we’re born with a nervous system that must wire itself up based on experience by selectively reinforcing some of the circuits while eliminating others.

“The nervous system could be built perfectly from the get-go, as perhaps it is in some lower animals,” Lichtman said. “The mammalian nervous system, however, allows an intelligent choice of what to maintain and what to get rid of.”

Lichtman comes to Harvard from Washington University Medical School, St. Louis, where he was a professor of neurobiology and where he had been a faculty member since 1983. He received a bachelor’s degree from Bowdoin College in 1973 and both an M.D. and Ph.D. in neurobiology from Washington University in 1980.

In collaboration with Professor of Molecular and Cellular Biology Joshua Sanes, who also recently came to Harvard from Washington University, Lichtman has worked out a way to directly label and observe the formation and reorganization of synapses.

Lichtman and Sanes have developed specially bred mice whose nerve axons glow in different colors. Using these mice and painless methods of anesthesia, Lichtman has watched these battles between nerve endings over days, weeks, and months, gaining a real-time understanding of what’s happening.

Department of Molecular and Cellular Biology Chairman Andrew Murray said Lichtman’s presence further strengthens the department’s robust neuroscience program.

“Jeff is a fantastic addition to our community,” Murray said. “He has made crucial contributions to how we think about the way nerve cells make connections to their targets. He will be a valuable addition to our already strong community of neuroscience, and his unrivaled expertise in developing new techniques for looking at cells and organs will be a huge boon for the entire department.”

The next step, Lichtman said, is to take this research to the central nervous system, which includes the brain and spinal cord and which is much more difficult to access and study.

“As wonderful and accessible as the neuromuscular system is, the brain is the opposite,” Lichtman said.