Studies in modified mice suggest that it is harder to make new long-term memories as we age because the brain is full of old ones that are hard to erase.
Mice whose brains were genetically modified to resemble those of adult humans showed no decrease in the ability to make the strong synaptic connections that enable learning — a surprise to neuroscientists at the Medical College of Georgia at Georgia Regents University, whose findingsappear in the journal Scientific Reports.
Yet as the modified mice entered adulthood, they were less capable of weakening connections that already existed, and that made it hard for them to form robust new long-term memories. Think of it as writing on a blank piece of white paper versus a newspaper page, said the lead author, Joe Z. Tsien. “The difference is not how dark the pen is,” he said, “but that the newspaper already has writing on it.”
The researchers focused on two proteins — NR2A and NR2B — long known to play a role in the forging of new connections in the brain. Before puberty, the brain produces more NR2B than NR2A; in adulthood, the ratio reverses.
By prodding mice to produce more NR2A than NR2B, effectively mimicking the postpubescent brain, scientists expected the subjects to have trouble forming strong connections. Instead, the mice showed no trouble creating new short-term memories, but brain scans showed that they struggled to weaken the connections that had formed older long-term memories.
“What our study suggests,” Dr. Tsien said, “is that it’s not just the strengthening of connections, but the weakening of the other sets of connections that creates a holistic pattern of synaptic connectivity that is important for long-term memory formation.”