Throughout life, new neurons are generated in the hippocampus, where they form a structure that supports memory creation. When new neurons are integrated into the hippocampus, they compete with existing cells, forging new synaptic connections that may weaken or replace older ones. As a result, high rates of hippocampal neurogenesis may drive the loss of information stored in existing circuits—i.e., forgetting. In many species, including mice and humans, rates of hippocampal neurogenesis are high during infancy and decline markedly over time. Consistent with the idea that hippocampal neurogenesis and forgetting are positively correlated, infancy in these species is also characterized by the absence of long-term memory formation. The correlation piqued the interest of Sheena Josselyn and Paul Frankland, neuroscientists at the University of Toronto and Hospital for Sick Children (both in Toronto, Canada): “This inverse relationship between the levels of neurogenesis and the ability to form a long-term memory got us thinking that maybe one is due to the other,” Josselyn told The Scientist.

Credit: Emilia Stasiak/Hemera/Thinkstock

Josselyn and Frankland's team carried out experiments to assess whether hippocampal neurogenesis regulates forgetting. Rodents were placed in a distinctive box where they received electric shocks and hence learned to fear the box. The team then manipulated neurogenesis in the rodents either pharmacologically or by providing access to running wheels (running enhances neurogenesis). The rodents were later returned to the box, and their reactions were observed (Science 344, 598–602; 2014). Freezing, considered a fear response, is a common reaction and indicates that the rodents remembered their previous negative experience with the box.

Providing access to a running wheel and pharmacologically increasing neurogenesis both curtailed freezing behavior in mice, suggesting that the mice had forgotten their previous negative experience. Furthermore, pharmacological inhibition of neurogenesis in mice with running wheels and in infant mice increased freezing behavior, suggesting that limiting neurogenesis improved memory retention. The researchers also studied guinea pigs and degus, which have lower rates of neurogenesis during infancy than do mice or humans. Guinea pigs and degus remembered the box for much longer than did mice, but boosting neurogenesis (either pharmacologically or by providing access to a running wheel) induced them to forget.

The results show that neurogenesis can disrupt established memories and that increasing neurogenesis can induce forgetting. The findings support the idea that there is a trade-off between formation of new memories and retention of existing ones. As Josselyn points out, “forgetting is an important part of healthy memory.”