Home Virginia Tech researcher’s early work helped set the stage for future neuroscience studies

Virginia Tech researcher’s early work helped set the stage for future neuroscience studies


healthcareThe field of neuroscience was still in its infancy when Michael Friedlander and his colleagues brainstormed a new experimental approach to examine how temperature change affects the entirety of a living organism. The resulting paper, published nearly four decades ago, was recently cited as a landmark example of temperature acclimation brain research.

“This is one of the very best papers ever published on the acclimatory responses of fish to change in temperature,” said George Somero, professor emeritus of biology at Stanford University and author of the classics article highlighting Friedlander’s research, which appeared in The Journal of Comparative Physiology in 1977. In January, Somero wrote his summary in a Journal of Experimental Biology section that was established more than a decade ago to highlight studies that shifted research paradigms.

Somero said he put Friedlander’s paper at the top of his “greatest hits” list when compiling studies that might warrant highlighting as a classic in the journal.

Friedlander, now executive director of the Virginia Tech Carilion Research Institute, was a graduate student at the time of the research, working in the laboratory of C. Ladd Prosser. A National Academy of Science member who was considered a giant in the field of comparative animal physiology, Prosser had studied temperature effects on animals for decades. He had recently become interested in the more subtle effects temperature could have on the nervous system and the brain.

In Prosser’s laboratory, Friedlander worked alongside postdoctoral fellow Andrew Cossins, now a professor of functional and comparative genomics at the University of Liverpool. Cossins, an expert lipid biochemist, and Friedlander, a neurophysiologist, decided to combine their research approaches to study how the brain adapts to different temperature changes in fish.

“Fish are generally unable to regulate their own internal core and brain temperature the way mammals do,” Friedlander said. “But, as vertebrates with complex nervous systems and behaviors, they have a remarkable capacity to adapt across a range of temperatures, spanning over 80 degrees Fahrenheit, depending on the species.”

The mammalian brain, including the human brain, in comparison, generally experiences changes of only about one degree Fahrenheit, according to Friedlander. Changes of five degrees in either direction can be devastating and even life threatening. Mammals have developed the ability to regulate their core internal temperatures with incredible precision, regardless of how drastic an environmental temperature change they experience.

“Unlike mammals, fish do not have the ability to maintain a constant core temperature,” said Friedlander, who also serves as Virginia Tech’s associate provost for health sciences. “Their internal temperature more or less follows the ambient water temperature of their surroundings, which varies daily and seasonally. Each fish species has certain genetic limits to its functional temperature range and a certain ability to acclimate across that range.”

Friedlander, Cossins, and Prosser selected a single species – the common goldfish – to determine the functional thermal limits of its brain and the mechanisms that define those limits. They acclimated goldfish along a 36-degree-Fahrenheit temperature range, analyzing the molecular composition and the electrical signaling properties of the brain’s nerve cells while also observing the behavior of the fish. Such an approach was unusual for that period, Friedlander said, but they were successful in defining a relationship between the effects of temperature on molecules, cells, and behavior.

The researchers found that temperature change affected the flexibility of molecules in the sheathing membranes of nerve cells, as well as the patterns of electrical signaling generated in those cells, leading to dramatic effects on the animals’ behavior. It was a revolutionary understanding at a time in which scientists were just beginning to see the parallels between molecular, physiological, and behavioral systems.

“It’s rare for any study of temperature acclimation to combine work on behavior with detailed studies of cellular physiology and biochemistry,” Somero said.

Almost 40 years after the goldfish study was published, Friedlander’s own research team will conduct a similar project this year in Antarctica, using notothenioidei fish. Genetically different than goldfish, notothenioidei are capable of living close to the extreme limit of vertebrate brain function and life – just below freezing, at least partially due to the presence of antifreeze molecules in their blood.

“In the context of today’s warming environment, particularly in the southern ocean surrounding Antarctica, very subtle changes in the ambient temperature of fishes can cause changes that manifest in a dramatic way, particularly in the brain, and resulting behaviors that are necessary for survival,” Friedlander said.

Although the animal may survive temperature changes, Friedlander added, the biological effects could lead to larger behavioral problems, such as rendering an animal unable to reproduce or gather food.

“It doesn’t take much to have an effect manifest behaviorally, and that can have a profound effect on the overall viability of a species,” Friedlander said. “This kind of experiment models the things that can happen in the real world as ocean temperatures increase.”

Somero, who has worked with notothenioidei fish himself, is looking forward to seeing the results of Friedlander’s upcoming research in Antarctica.

“I can’t wait to see what he discovers,” Somero said.



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