Squid Research Unlocking Brain’s Mysteries

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Jay Lindsay, Associated Press

Published — Wednesday 15 October 2003

Last Update 15 October 2003 3:00 am

FALMOUTH, Massachusetts, 15 October 2003 — The 75-foot (22.5-meter) squid boat takes a gentle turn toward a Woods Hole pier on a summer afternoon, its nets filled with an animal whose primitive nervous system holds the secrets of the human brain.

Loligo’s skipper watches under a hot sky, the squid expelling jets of water as a deckhand scoops them from the boat for transport to the Marine Biological Laboratory, just a few hundred meters away.

From the time of delivery, Professor George Langford knows he has a few hours, tops, to get his squid dissected so he can continue researching the mysteries of how the brain remembers, and what makes it forget when a disease such as Alzheimer’s takes hold.

For 31 years, Langford’s studies have revolved around squid nerve fibers, called giant axons, that are several times larger than a human’s and offer unparalleled opportunities for observation and experimentation. The squid axon is so useful in the general study of nerves that some joke the squid deserves a Nobel Prize for its contributions to science.

Langford’s progress has been quiet and steady over the decades as he seeks no less than cures to various degenerative brain diseases.

“It’s part of what drives me in my research,” the Dartmouth biology professor said. “It’s really understanding the basic process that’s going on and using that information to try to solve human diseases.

Langford’s Woods Hole lab is on the third floor of a nondescript building that overlooks the harbor and its steady traffic of fishing and research vessels.

The hallway is lined with refrigerators filled with the chemicals used in various experiments. Just down the hall, a Spartan room houses the equipment that Langford’s student research intern, John Delacruz, uses to remove the squid’s giant axon. If the squid aren’t dissected within 10 hours of delivery, they bang themselves against the holding tank walls so relentlessly that the giant axons are useless.

The squid’s giant axon is essentially a bundle of nerve fibers that carry electrical impulses to a muscle that contracts and propels the squid through the water.

Though the human axon is much smaller, more complex and carries the signals more quickly, at its base the systems are the same, and what’s learned in squid can apply to humans. “It shows that as all of us evolved, certain basic functions have remained constant, from the smallest animal to the most complex,” Langford said. “That’s one of the principles that brings all of biology together.”

Scientists know squids remember — the animals recognize predators and even respond to shapes that look like predators.

They also know a squid’s brain, like a human brain, is “plastic,” meaning it’s not hard-wired like a computer. Rather, the connections in the brain are changing constantly as messages are carried by molecules and stored.

For those connections to occur, the “skeleton” that helps the cell keep its structure — called the cytoskeleton — must change shape so the cell can link with other cells. The connections also depend on packets of information pushed within this skeleton by different types of “molecular motors.”

A malfunction in the cytoskeleton during these connections can cause problems such as a loss of memory. So if Langford can identify the proteins in the cell skeleton, he can tell what proteins are present or absent when the motors aren’t delivering information properly.

Even if all the proteins working in the cytoskeleton can be identified, Langford’s job wouldn’t end there.

“If we know what the protein is, you ultimately have to show how it functions,” Langford said. “You can say this protein is missing, and it causes loss of memory, (but) you still have to connect the dots.”

Thomas Pollard, a biology professor at Yale University who has worked with Langford at Woods Hole, said Langford’s most important contribution has been his discovery of previously unknown molecular motors, which seem to be part of a network that carries content shorter distances within the axon. “It’s like a transportation system,” Pollard said. “Before George’s work, people had focused on sort of the interstate highways, and his work shows there’s probably a local transportation system, like within a city.”

Without an awareness of this secondary travel system, scientists could never completely understand what’s happening when connections break down, he said.

Langford’s work takes endless experimentation using varying levels of chemicals in different concentrations and over different time frames. All during the academic year, Langford and his group of five to six students and assistants prepare for the 12 weeks of 12 hours days with the squid at Woods Hole. Students bunk together in dorm rooms near the labs, and work in the tight quarters in the lab. It is, said Delacruz, sort of a “biology bootcamp.”

For Langford, summer is a time when his intellectual energy is at a peak. The concerns of campus life are replaced with a single-minded devotion to his work, done in the midst of a unique gathering of biologists from all over the country.

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