For decades researchers have known that our ability to remember everyday experiences depends on a slender belt of brain tissue called the hippocampus. Basic memory functions, such as forming new memories and recalling old ones, were thought to be performed along this belt by different sets of neurons. Now findings suggest that the same neurons in fact perform both these very different functions, changing from one role to another as they age.

The vast majority of these hippocampal neurons, called granule cells, develop when we are very young and remain in place throughout our lives. But about 5 percent develop in adulthood through the birth of new neurons, a process known as neurogenesis. Young granule cells help form new memories, but as they get older they switch roles to helping recall the past. Newer granule cells pick up the slack, taking on the role of helping to form new memories. Susumu Tonegawa of the Massachusetts Institute of Technology and his colleagues published the findings on March 30 in the journal Cell.

Tonegawa’s team tested the role of these adult-born cells by genetically engineering mice in which the old cells could be selectively turned off. They then put the mice through a series of mazes and fear-conditioning tests, which demonstrated that young granule cells are essential to forming separate memories of similar events, whereas old granule cells are essential to recalling past events based on small cues. This discovery suggests that memory impairments common in aging and in post-traumatic stress disorder may be connected to an imbalance of old and new cells. “If you don’t have a normal amount of young cells, you may have a problem distinguishing between two events that would be seen as different by healthy people,” Tonegawa says. At the same time, the presence of too many old cells would make it easier to recall traumatic past experiences based on current cues.

Previous research has shown that both traumatic experiences and natural aging can lead to fewer new neurons being produced in the hippocampus. But a cause-and-effect relation between impaired neurogenesis and memory disorders has yet to be established. If such a connection is found, this research will have opened the door to a novel class of treatments aimed at stimulating neurogenesis. Already it is changing the way we think memory works.

This article was published in print as "Old Neurons, New Tricks"