Decision letter: Adult-born granule cells mature through two functionally distinct states

Abstract

Remembering what happened on different occasions involves a process in the brain called pattern separation, which allows us to separate and distinguish our memories. One part of the brain where pattern separation occurs is called the dentate gyrus, which sits in the hippocampus—the brain region that is in charge of certain forms of learning and memory. Neurons called granule cells are thought to play a central role in hippocampal pattern separation. These cells, unlike the majority of nerve cells, can form at any time, and those that form in the mature brain are called adult born granule cells (ABGCs). Although it usually takes 10 weeks for these cells to fully mature, they are capable of communicating with each other about 3–4 weeks after being generated. Previously, it had been reported that while young, 4-week-old ABGCs are required for pattern separation, slightly older (8 week old) ABGCs are not. What intrinsic properties make ABGCs capable of contributing to pattern separation? Is this property defined by the fate (i.e. a predetermined program) of the cell, or by the cell's experiences and activities? To investigate these questions, Brunner et al. labeled ABGCs with a fluorescent tag when these neurons were born in adult male rats. Then, when the tagged cells were aged between 3 and 10 weeks old, the electrical properties of the labeled cells were measured from thin brain slices. Brunner et al. found that ABGCs respond to input signals with two different levels of sensitivity. The youngest cells (3–5 weeks old) are exceptionally sensitive to a narrow range of input signal strengths, which is useful for pattern separation. The oldest investigated cells (10 weeks old), on the other hand, respond incrementally to a wide range of different input signal strengths. Under these experimental conditions, the cells changed how they respond to input signals some time between 5 and 9 weeks after being born. However, they either behaved like the youngest or like the oldest cells: no intermediate behavior was seen. Unexpectedly, the switch is not directly related to the age of the cells: cells born at the same time don't necessarily change behavior at the same time, and cells born at different times may behave similarly. Thus, Brunner et al. suggest that it is the experience of the cells, and not their fate, that determines how they help the dentate gyrus function during the investigated period.