Alcino J. Silva at UCLA, Paul Frankland (now at University of Toronto) and coworkers at UCLA have discovered that the anterior cingulate of the cortex of the brain plays a key role in the formation and recall of long term memories.
First, the scientists engineered mice with a mutant form of a gene called kinase II, which eliminates the ability to recall old memories. The animals were trained to recognize a cage, then tested for their memory of the cage at one, three, 18 and 36 days after training.
"We found that the mutant mice recognized the cage for up to three days after training, but their memory of the cage disappeared after 18 and 36 days," Silva said. "While they possessed short-term recall, they never developed a distant memory of the cage."
Earlier research suggested that the cortex — or outer layer of the brain — plays a role in the storage and retrieval of old memories.
Once memories became weeks old their recall caused the anterior cingulate to light up in brain scans.
In their second strategy, the UCLA researchers used imaging methods to track visually which regions of a normal mouse's cortex grew active during memory testing.
No part of the cortex lit up when the animal was exposed to the cage one day after training. When the mouse saw the cage 36 days after training, however, the images highlighted a part of the cortex called the anterior cingulate.
"We were fascinated to see the anterior cingulate switch on when we tested the normal mice for distant memory, but not when we tested them for recent memory," Silva said. "In contrast, the mutant mice's anterior cingulate never switched on during tests for distant memory.
"This result suggests that the kinase II mutation disrupted processes in the anterior cingulate that are required for recalling distant memories," he said.
Disabling the anterior cingulate appears to selectively prevent access to older memories.
Third, the UCLA team injected normal mice with a drug that temporarily turned off the anterior cingulate. The scientists discovered that disabling the anterior cingulate did not disrupt the animals' memory of the cage at one and three days after training, but did interrupt the mice's memory of the cage at 18 and 36 days after training.
"When we silenced the anterior cingulate, the mice kept their recent memory of the cage, but lost their distant memory," Silva said. "This was consistent with our two earlier findings.
"We now had several pieces of evidence all pointing to the same conclusion," he said. "The anterior cingulate plays a special role in keeping our early memories alive. Our work with the mutant mice also suggests that kinase II is critically involved in preserving our oldest memories."
When a person recalls a memory, Silva theorizes, the anterior cingulate rapidly assembles the signals of the memory from different sites in the brain.
"If the anterior cingulate malfunctions, a recalled memory may be too fragmented to make sense to the person," Silva said. "It's like a puzzle with missing pieces. This could be what occurs during dementia."
The formation of new memories is thought to involve the strengthening of synaptic connections between groups of neurons. Remembering involves the reactivation of the same group, or network, of neurons. As memories age, the networks gradually change. Initially, memories for everyday life events appear to depend on networks in the region of the brain called the hippocampus. However, over time, these memories become increasingly dependent upon networks in the region of the brain called the cortex.
"We believe there is active interaction between the hippocampus and cortex, and that the transfer process of memories between these two regions in the brain occurs over several weeks, and likely during sleep," added Dr. Frankland, holder of the Canada Research Chair in Cognitive Neurobiology.
Curiously, this points to a deficiency in how schools and colleges test for knowledge. If students learn something a week before finals then what they are being tested on is their short term memory version of their knowledge of the material. If the goal is to test for long term memory it really becomes necessary to test for the knowledge more than once with weeks between the tests.
Also, drugs and other methods of enhancing long term memory formation must enhance processes in the brain that occur over a period of weeks.
This builds on some work done at MIT which found that a kinase mutation in mice blocked the ability to form long term memories.
|Share |||Randall Parker, 2004 May 07 02:41 AM Brain Memory|