Turning Astrocytes from the Rostral Migratory Stream into Neurons: A Role for the Olfactory Sensory Organ

Neurogenesis persists within a few restricted areas of the adult mammalian brain, giving rise to neurons that functionally integrate into preexisting circuits. One of these areas, the subventricular zone (SVZ), was believed, until recently, to be the unique source providing the adult olfactory bulb (OB) with newborn neurons. Because of the fact that neuroblasts derived in the SVZ migrate through the rostral migratory stream (RMS) en route to the OB, the existence of candidate neural stem cells within the RMS was long overlooked. Here, we confirm and considerably extend recent evidence for the existence of adult neural stem cells within the RMS, and go on to investigate their proliferative regulation. Specifically targeting RMS-astrocytes with lentiviral vectors encoding GFP, we demonstrate that glial cells in the RMS differentiate into both OB granule and periglomerular interneurons. In addition, ultrastructural analysis unambiguously reveals the astrocytic nature of stem cells in the adult RMS, and patch-clamp recordings demonstrate the functional integration of RMS-derived interneurons into OB circuitry. Proliferative regulation was investigated via two contrasting manipulations: exposure to an odor-enriched environment that enhances candidate stem cell proliferation in both the RMS and SVZ, and chemical lesion of the main olfactory epithelium that increases cell proliferation in the RMS only. New neurons in the adult OB can therefore arise from different neurogenic areas that can be separately regulated.