Optical controlling reveals time-dependent roles for adult-born dentate granule cells

Accumulating evidence suggests that global depletion of adult hippocampal neurogenesis influences its function and the timing of the depletion impacts the deficits. However, behavioral roles of adult-born neurons during their establishment of projections to CA3 pyramidal neurons remain largely unknown. Here we combined retroviral and optogenetic approaches to birth-date and reversibly control a group of adult-born neurons in adult mice. We show that adult-born neurons form functional synapses on CA3 pyramidal neurons as early as 2 weeks after birth, and that this projection to the CA3 area becomes stable by 4 weeks in age. Newborn neurons at this age exhibit enhanced plasticity compared to other stages. Notably, we found that reversibly silencing this cohort of ~4 week-old cells after training, but not cells of other ages, substantially disrupted retrieval of hippocampal memory. Our results identify a restricted time window for adult-born neurons exhibiting an essential role in hippocampal memory retrieval.