Studying ‘business end of nerve cell’

To Joshua Sanes, the synapse where a nerve delivers messages to a target cell is a marvel of nature.

Durable and reliable, the same synapses can work throughout a person’s life, delivering as many as 100 messages each second to nerve or muscle cells.

Yet the structures are also flexible and capable of modification to meet changing conditions.

“They can last a lifetime, yet change in a day,” Sanes said. “They have the property of amazing reliability. If you live to 100, you may have the same synapses for 100 years.”

That sense of wonder has kept Sanes’ attention fixed on synapses for decades, since his graduate student days at Harvard, when his interest in psychology and mental illness led him into the budding field of neurobiology.

The synapse itself is the business end of a nerve cell, which is the basic unit that makes up the body’s nervous system. Synapses are located on long extensions called axons, which reach out from nerve cells to make contact with either other nerve cells or with target cells such as muscles.

The synapse is the site at which signals are sent to the next cell through chemicals called neurotransmitters, which carry signals across a tiny gap, passing them on through the body until they reach the intended target cell.

Nerve cells make up the brain and the spinal cord, and, strung end to end like an electrical network, carry signals throughout the body and back again. The cells and their signals guide everything from thought to movement to emotion to the perception of smells and the reading of a newspaper.

For Sanes, appointed July 1 as a professor of molecular and cellular biology and the new director of the Center for Brain Science, his often groundbreaking work on synapses hasn’t directly led to answers about the mental illnesses he was initially interested in.

But work conducted by Sanes and others in recent decades has created a broad-based foundation for unprecedented interdisciplinary collaboration that Sanes said will allow today’s students to perhaps answer some of the most profound questions about how the brain and the nervous system function – and malfunction.

Sanes came to Harvard from the Washington University School of Medicine in St. Louis, where he was Alumni Endowed Professor of Neurobiology. He had been at Washington University since 1980, when he was named assistant professor of physiology and biophysics. Sanes is not a stranger to Harvard. He received master’s and doctorate degrees in neurobiology from Harvard in 1976 and conducted postdoctoral study at Harvard Medical School in 1977.

Sanes said he is excited by the possibilities offered by the new Center for Brain Science, which will bring in new faculty members as well as foster new interactions among existing researchers in related fields across the University.

“The idea is to bring together people in a number of disciplines who don’t normally interact, to address problems in systems neuroscience,” Sanes said.

The center’s overarching goal is to understand better how the nervous system is linked to behavior. It will do that through three major avenues of inquiry, Sanes said.

First is to map the body’s wiring, the neural circuits, that underlie behavior. Sanes said such an effort would be broad-based and use whatever methods researchers can develop to achieve that goal. He said the effort could unify biologists with engineers, psychologists, and other specialists for projects involving everything from visual imaging to electrical measuring to computer modeling and a host of approaches in between.

Moreover, researchers would use whatever organism they found appropriate to further their research. Understanding the complex behavior of ants as it relates to ant nervous systems, Sanes said, could shed considerable light on the links between nervous circuitry and behavior.

The second avenue of inquiry, Sanes said, would be to find the biological basis of individual differences in behavior. The inquiry would explore whether differences in individual behavior are related to how the body is wired and whether behavioral differences can be traced directly to differences in an individual’s nervous system.

“How an ant navigates to its hive is really quite an amazing behavior,” Sanes said. “It’s a good bet that the wiring diagram for something like that would have a lot of similarities to the wiring diagrams that explain some human behaviors – navigation, for one, but probably lots of others as well.”

The center’s third effort will be focused on building the appropriate tools to further its research. Sanes said it is likely that an array of new equipment and techniques, such as microscopes and imaging processes, will be needed for the effort to be successful. Computational and theoretical tools will also be needed.

As he builds the center, Sanes’ own research will continue. His current research seeks to understand how synapses in the peripheral nervous system form their marvelously reliable and flexible connection and how they operate at the molecular level.

“We’re in a position to ask detailed molecular questions about how they work,” Sanes said.

He is also increasingly exploring how nerve cells in the brain know which other cells to form synapses with. For example, a nerve cell wired to the part of the brain responsible for processing visual signals forms synapses with cells related to the eye while ignoring nearby cells related to hearing.

“How does an axon choose the right few out of all cells with which to make a synapse?” Sanes said. “It’s that kind of specificity that we study. And maybe what we learn about development will help us understand the adult circuit, too – the mission of the center.”

Sanes said he’s excited about the future for research at the center. The time is ripe, he said, for collaborations across disciplinary boundaries as researchers seek expertise and techniques in different fields that can help them answer basic questions in their own. And it is a place like Harvard, Sanes said, with unique strength in many related fields, such as biology, engineering, neurology, and psychology, that can foster those collaborations.

“It is a chance to exploit what people like me have done over the years to understand [neural] systems and come back up and understand how they affect behavior,” Sanes said.