Maturation and death of adult-born olfactory bulb granule neurons: role of olfaction.

Young neurons born in the subventricular zone (SVZ) of adult mice migrate to the olfactory bulb (OB) where they differentiate into granule cells (GCs) and periglomerular interneurons. Using retroviral labeling of precursors in the SVZ, we describe five stages and the timing for the maturation of newly formed GCs: (1) tangentially migrating neuroblasts (days 2-7); (2) radially migrating young neurons (days 5-7); (3) GCs with a simple unbranched dendrite that does not extend beyond the mitral cell layer (days 9-13); (4) GCs with a nonspiny branched dendrite in the external plexiform layer (days 11-22); and (5) mature GCs (days 15-30). Using [3H]thymidine, we show that the maximum number of labeled GCs is observed around day 15 after injection. Interestingly, between days 15 and 45 after birth, soon after the cells developed spines, the number of [3H]thymidine-labeled GCs declined by 50%. Using anosmic mice, we found that sensory input was critical for the survival of GCs from day 15 to 45 after labeling. However, the number and morphology of 15-d-old cells in the granule cell layer was similar in anosmic and wild-type mice. We infer that the lack of activity did not have an effect on the generation, migration, and early differentiation of granule cells. Soon after young GCs matured, and presumably became synaptically connected, their survival depended on the level of activity that they received. This selection mechanism might allow the construction of specific OB circuits based on olfactory experience and suggests possible functions of OB cell replacement.