October 07, 2004
Brain Circuit May Permit Scientists to Eavesdrop on Memory Formation
Howard Hughes Medical Institute researchers have identified a
circuit in the brain that appears crucial in converting short-term
memories into long-term memories. The circuit links the major
learning-related area of the brain to another region that governs the
brain's higher functions.
The studies open the way for eavesdropping on one of the central
processes in learning and memory, says HHMI investigator Erin M.
Schuman. She and graduate student Miguel Remondes of the California
Institute of Technology published their findings in the October 7,
2004, issue of the journal Nature.
“These data suggest that the importance of the neocortex as a memory storage site increases with the lifetime of the memory.”
Erin M. Schuman
According to Schuman, the finding sheds light on a central question
in learning and memory research that concerns the roles of two brain
structures, the hippocampus, which is involved in memory formation, and
the neocortex, which is associated with higher brain functions.
“There are two key findings required to understand the present
work,” said Schuman. “First, lesions of the hippocampus
prior to training can prevent the formation of some kinds of short-term
memory. Second, if one delays the hippocampal lesion to days after
training, one can observe that as the delay increases, the memory
deficit decreases. These data suggest that the importance of the
neocortex as a memory storage site increases with the lifetime of the
memory. In addition, there is a clear need for the hippocampus and
cortex to talk to one another.”
One candidate for the communication conduit is the temporoammonic
(TA) projection, “a pathway that we have been chipping away at
understanding for years,” said Schuman. “We and others had
studied the physiology of this very direct connection between the two
areas, but no one had directly studied this pathway's importance in
learning.”
For the experiments, Remondes perfected a technique to make precise
electrical lesions of the TA projection in the brains of rats. In the
first set of experiments, he created the lesions in animals and then
tested their ability to learn to navigate a tank full of opaque water
to find a submerged platform. When the researchers tested the rats the
day after the electrical lesions were made, they still recalled the
platform's location. But they lost that memory four weeks after
training.
“There were two possible explanations for this result,”
said Schuman. “Either we had selectively impaired the process of
converting short-term memories into long-term memories. Or, short-term
and long-term memories are on parallel pathways, and the lesion had
selectively affected the long-term memory pathway.”
So, in a second set of experiments, the researchers created the TA
lesions in animals 24 hours after they had learned the position of the
platform. These animals still retained short-term memory; but four
weeks later they lost that memory as well. Since the lesion was made
after learning, this experiment suggested that the animals had problems
converting their short-term memory into a long-term memory — a process
also called consolidation.”
“If this really was a process of memory consolidation, it
implies that there's a window of vulnerability that will close,”
said Schuman. “Thus, in the last experiment, we waited three
weeks for the memory to consolidate and then made the lesion. When
tested a week later, a majority of the animals remembered the platform
location even though they had just received the lesion; that is, it
appeared that they had already adequately consolidated the memory in
the three weeks post-training prior to the lesion.
“These experiments tell us that the TA projection is an
important part of the dialog between the hippocampus and the cortex
that occurs after learning,” said Schuman. “Now, what is
needed is an exploration of the specific firing patterns of neurons
that make up the TA projection during learning and the consolidation
period. It's interesting that a lot of the important activity likely
takes place off-line, when the animal is removed from the direct
behavioral experience.”
Future studies could give insight into whether sleep plays a role in
memory consolidation, a theory that has been proposed by many
researchers, said Schuman. Studies by other researchers have shown that
there is distinctive coordinated brain activity between the hippocampus
and neocortex during sleep, she said.
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