First real-time view of developing neurons reveals surprises, say Stanford researchers

March 23, 2005

STANFORD, Calif. - Scientists have believed that neurons need a long period of fine-tuning and training with other neurons before they take on their adult role. But after using new technology for the first time to watch these cells develop, a team of researchers at the Stanford University School of Medicine found that neurons come into this world with a good idea about what they'll become as adults.

The work, which is detailed in a paper in the March 24 issue of Neuron, took place in the brain of a small see-through fish called a zebra fish. Stephen Smith, PhD, professor of molecular and cellular physiology, and graduate student Christopher Niell immobilized a young fish at an age when the nerves first grow from the eye to reach the brain. Then, with the aid of a 6-foot-long laser and some fancy microscopy, the researchers were able to watch individual neurons as they matured in real time.

The pair specifically monitored hundreds of neurons in the region of the brain that respond to images. Niell set up a tiny LCD screen showing squares the size of the fish's favorite planktonic food moving up and down or left and right.

They expected to find that young neurons fire in response to a variety of different images, then refine their role over time so that in the adult fish the neurons only respond to images moving in a certain direction or near the left or right side of the visual field.

What they found was a surprise. As soon as the neurons were old enough to respond to the LCD screen, they specifically fired when they sensed only one type of movement. When the tiny square moved left to right, a distinct population of neurons turned fluorescent colors to indicate their activity. Moving the square the reverse direction triggered a different population of neurons to light up.

"At first we felt like we let some air out of our own tires with this finding," said Smith. His previous work had supported the prevailing idea that neurons need a period of fine-tuning before establishing their final identity.

Still, the experiments mark the first time researchers have been able to watch neurons in an entire region of the brain as they fire one by one in real time. The technical savvy involved in monitoring neurons will allow researchers to conduct experiments that were previously not possible.

While the research showed neurons firing in a more mature way than expected, it also revealed that neurons take their time establishing the final wiring of the brain. Young neurons send out branches in all directions in the hopes that some branches will connect to other neurons and form synapses that transfer information. As the neuron matures, some of these branches form stable synapses while others recede. This trial-and-error process is what establishes the final interconnected mesh of the brain.

Because the group could see the full branching structure of a neuron each time it fired, they could watch the branches grow and recede like a tree waving in the wind, losing the occasional twig. Over time, the network of branches stabilized into the mature form.

"We're looking at a dynamic process that nobody has ever seen before," Smith said.

Understanding how neurons mature into their adult role goes beyond zebra fish and their ability to see their eventual planktonic prey. "Probably these same processes are happening in our own brains all the time," Niell said. When people learn new skills or add memories to their overstuffed brains, new connections are required to retain that information.

Some diseases also seem to be caused by brain connections not forming normally. Dyslexia, for example, may be caused by connections failing to form between certain brain regions, whereas schizophrenia may result from too many connections forming.

What's more, any cure for spinal cord injuries will require new neurons to form the appropriate connections.
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PRINT MEDIA CONTACT: Amy Adams at (650) 723-3900 (amyadams@stanford.edu)
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Stanford University Medical Center integrates research, medical education and patient care at its three institutions - Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children's Hospital at Stanford. For more information, please visit the Web site of the medical center's Office of Communication & Public Affairs at http://mednews.stanford.edu.

Stanford University Medical Center

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