Remember the old myth that people only use 10 percent of their brains? Although a new study confirmed that bromide to be apocryphal, it did find that we may only use 20 percent of the nerve cells in our midbrain to form memories.
Researchers at the University of California, Los Angeles, and The Hospital for Sick Children in Toronto monitored neurons in the lateral amygdalae (two almond-shaped regions on either side of the midbrain associated with learning and memory) of mice to see whether the presence of the CREB (cAMP response element binding) protein plays a key role in signaling brain cells to make memories. CREB, a transcription factor that typically increases the production of other proteins in cells, is believed to be involved in memory formation in organisms from sea slugs to humans. Scientists hope that their findings, reported in the current issue of Science, may help pave the way to new treatments for Alzheimer's Disease.
Researchers injected a vector designed to return CREB production to normal in mice that had been genetically modified to underproduce the protein. After being injected, these mice, who also were memory-impaired, performed as well as normal mice in memory tests. During the trials, researchers played a sound and then shocked the animals; when the sound was played again, normal mice and those with rescued CREB function froze—for a certain[short?] period of time—a reaction typical of fear.
When the researchers later dissected the mice's brains, they found that the fluorescent probes they had attached to the CREB vectors showed they had affected only about 20 percent of the neurons in the lateral amygdala. "That surprised us. We thought that we would have to affect a lot more neurons in order to see a big change in memory," says study co-author Sheena Josselyn, a neurophysiologist at The Hospital for Sick Children. "Not all [neurons] participate in every memory. Maybe we're biasing these neurons to participate in this memory and [CREB is] all you need'' to compel it."
To determine if the CREB-producing cells were involved, the scientists then tried to follow the memory-making process by inserting a probe, which would give off a fluorescent tag if RNA from a gene known as Arc had recently been transcribed in brain cells. Arc levels are normally low in a cell but increase considerably when neuronal activity has taken place. The RNA is transcribed in the nucleus of a cell and then transported through the cell's body to its dendrite, the projection of the neuron that receives information from other cells. "Arc RNA provides a really good molecular marker of when this neuron was active," says Josselyn. She adds that if the team found RNA in the nucleus of neurons immediately after a training event, they knew cells had been active within the last five minutes; if the probe was in the dendrite, they estimated activity had taken place 20 minutes earlier.
The team found CREB-enabled nuclei to be three times more likely to have the Arc signature in them than nuclei in CREB-impaired neurons. The researchers also tested normal mice that were injected with a vector that would selectively decrease CREB function in some of their neurons. After running the fear-training trials again, they noticed that the mice learned normally, suggesting that the neurons unaffected by the CREB-reducing vector were still producing enough CREB to make the memories.
The results: the memory trace, signified by Arc, showed that activity had taken place in 20 percent of neurons. "We think that it's really a competition, that neurons are really battling it out" amongst each other to be involved in the memory-making process, says Josselyn. "It's like grading on a curve the same number [20 percent] of students are going to get As"—or in this case help make the memory.
It is the same percentage, but not the same neurons, however, that create each memory. Also, researchers are not certain what causes naturally boost CREB function and, therefore, the likelihood of any particular neuron participating in making a memory. But Josselyn speculates that the brain likely "differentiates different memories by having different neurons encode them."