Study Confirms Brain’s ‘Hard-Wiring’ of Memory
Researchers at USC and the University of Illinois have for the first time experimentally confirmed the long-standing theory that the brain stores memories by “hard-wiring” new connections between groups of brain cells.
Their results, to be reported today at a meeting of the Society for Neuroscience in Phoenix, are the culmination of decades of searching for the physical mechanisms underlying the mysterious process by which the brain stores memories.
In two separate sets of experiments involving rats and rabbits, the researchers clearly identified memory-related changes in the physical links among groups of brain cells, or neurons. The changes occurred when the animals learned specific physical activities, such as blinking an eye in response to the ringing of a bell or learning to walk along an elevated pathway.
The experiments offer an explanation for why some types of learned behavior, such as the ability to ride a bicycle, are never forgotten. The reason is that the necessary muscle commands for riding a bicycle, for instance, are hard-wired into brain cells in the same way that some commands for operating a computer are permanently stored by physically wiring transistors together.
“In terms of vertebrates, we really haven’t had any direct information about anatomical change related to specific learning events,” said neuroscientist Lawrence R. Squire of the Veterans Affairs Hospital in San Diego. “This will greatly increase our level of certainty” about how memories are formed, he added.
Psychobiologists Richard F. Thompson of USC and William Greenough of Illinois have been studying a so-called Pavlovian response in rabbits. The technique is named after Russian physiologist Ivan Pavlov, who rang a bell every time he fed a group of dogs. After training, the dogs began to salivate every time the bell was rung, even if they were not given food.
Thompson rang a bell every time he directed a mild puff of air into one eye of rabbits, causing them to blink. After training, the rabbits would blink every time the bell was rung.
Implanting microelectrodes throughout the brain, Thompson and his colleagues found that the learned blinking was controlled by a small group of cells, called Purkinje cells, in the cerebellum, which is the brain’s coordinating center for muscular activity. (In previous experiments Thompson found that when he surgically removed the small group of Purkinje cells, the animals no longer blinked.)
Thompson then turned the trained animals over to Greenough, whose specialty is looking for signs of increased connections between brain cells.
In previous studies with rats, Greenough had shown that rats raised in an “enriched” environment--one with lots of toys and other mentally stimulating objects--have a much greater number of intercellular connections than those raised in a more sterile environment. In those cases, however, the increased connections could not be associated with specific memories.
In the new study, Greenough and his students studied the number of intercellular connections in the specific area of the cerebellum that Thompson had shown controlled the eye-blink behavior. They compared the number of connections in this area to the number on the opposite side of the cerebellum, controlling the eyelid that was not trained, and found a significant difference.
In the 15 rabbits studied over a two-year period, “the differences were statistically reliable and clearly visible,” Greenough said in a telephone interview. “We really have isolated a case where, in brain cells that are clearly involved in the performance of a task, we have crystal-clear (structural) change that indicates a change in anatomical circuitry.”
The discovery of altered numbers of connections, Thompson added, “is not surprising, in that it fits theory, but there has been no particular evidence (to support the theory) before. We were convinced there would be something like this because memories are never forgotten.”
The cerebellums of all mammals are remarkably similar, Greenough noted, and researchers are confident that discoveries made in animal brains are applicable to humans. They also believe that the mechanism used for storing memories involved with muscle movements will be similar to, if not identical to, those involved in storing other types of memories.
In a separate set of experiments, Greenough trained 19 rats to walk an elevated pathway. At the beginning of the training, the pathway was four inches wide and solid, but by the end of the training period, it was composed of slack ropes or chains.
As controls, he used rats that walked on treadmills or voluntarily did other types of exercises, such as running in a ball. “In those cases, there was a lot of activity, but no learning,” he said.
When Greenough and his students examined the brains of the animals that had learned to walk the elevated pathways, they found changes similar to those found in the rabbits, but in a different group of cells in the cerebellum. Again, the conclusion was that the animals learned by establishing unique sets of connections among the brain cells that control the movements.
Their results suggest, Thompson said, that “permanent memories, including experiences, involve these kinds of anatomical changes--not necessarily in the cerebellum, but someplace in the brain.” He also noted that the brain has the potential for “trillions and trillions” of such physical connections, so that the physical structure of the brain does not limit the number of things that can be remembered.
Both Thompson and Greenough caution that researchers are only beginning to unravel the mechanism of memory formation. “This is a major advance,” Greenough said, “but it is only a first step that leads to a lot more research rather than a last step that wraps everything up.”
