How Neurons Get a Little Help From Their Friends

Neuron

By Jacqueline Mitchell

Metaphors come easily to Phil Haydon. All the brain's a stage, and its neurons merely players, he Phil Haydonsays.

But it's the astrocytes--an abundant, but little understood type of brain cell--that Haydon suggests serve as stagehands, without which the play could not go on. As the Annetta and Gustav Grisard Professor and chair of the department of neuroscience at the medical school, Haydon is working to get these backstage cells the recognition they deserve and, in the process, to decode the language of the brain.

Ever since the Italian physicist Luigi Galvani discovered in 1771 that a spark will make a dead frog's leg twitch, neuroscience has focused on the electrically excitable neuron as the brain cell that deserves top billing. But that narrow attention on the neuron is really an artifact of technical limitations, Haydon says. "We always look under the light," he comments, not off to the darker sides where the less-obvious effects linger.

With an arsenal of high-tech tools, Haydon's team is now illuminating the electrically inactive brain cells that were largely overlooked by 20th-century neuroscience.The central nervous system, which includes the brain and the spinal cord, contains two types of cells. The first are neurons, which propagate electrical impulses via electrochemical communication--a stimulated neuron dumps a chemical cocktail of neurotransmitters into the space, called a synapse, between itself and its neighboring neurons. Those chemicals, inturn, provoke an electrical response from the surrounding cells. These actions and reactions happen extremely quickly; it's how your brain can whisk your hand off a hot stove before you've even consciously registered the heat.

Outnumbering neurons ten to one in the human brain, glial cells support and protectthe neurons. For decades, researchers thought that's all these cells--named for the Greek word for "glue"--did.

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But a surprising finding in Haydon's lab, reported in Nature in 1994, began to change that conventional wisdom. Haydon--then at Iowa State University--and his colleagues killed off the neurons in a sample of living brain tissue, expecting to block the release of chemical transmitters.

However, the team was surprised to find some of the chemical transmitters had been released anyway. "It must have been glial," says Haydon. "So we took a total risk and changed the direction of the lab."

The discovery was the first evidence that glia play a previously unknown role as modulators of synaptic activity. It was as though scientists who had been listening to one end of a telephone call suddenly were able to hear both sides of the conversation.

"Haydon's group really opened up a whole new line of research," says Harald Sontheimer, professor of neurobiology at University of Alabama, Birmingham, and director of the Center for Glial Biology in Medicine there. "People talked about the possibility that glial cells played a role, but Haydon has brought unprecedented credibility to the field."

A native of England, Haydon joined the faculty at Iowa State University as an assistant professor in 1986. In 2001, he moved to the University of Pennsylvania in Philadelphia, where he was a professor and vice chair of the neuroscience department. He came to Tufts last summer because "it was clear the administration was very serious about building a great neuroscience department that will be recognized for excellence," he says.

Tufts' neuroscience department can distinguish itself from its competitors by narrowing its research focus to synapses, brain disorders and neuro-glial interactions, says Haydon, who also plans to deepen collaboration with the departments of psychiatry, neurosurgery and neurology at Tufts Medical Center. "The spirit of cooperation here [at Tufts] is second to none," he says.

"And that is our opportunity and our challenge, to be competitive and driven, while protecting that collegiality."

Since that serendipitous research result in the early 1990s, Haydon's lab has used modern computing, powerful imaging tools and microscopy--and even genetic manipulation--to study these long-unheralded cells. He now focuses on one type of glial cell, called astrocytes, star-shaped cells that are often in close proximity to neuronal synapses.

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