Neural stem cells and the regulation of adult neurogenesis

Abstract

Presumably, the 'hard-wired' neuronal circuitry of the adult brain dissuades addition of new neurons, which could potentially disrupt existing circuits. This is borne out by the fact that, in general, new neurons are not produced in the mature brain. However, recent studies have established that the adult brain does maintain discrete regions of neurogenesis from which new neurons migrate and become incorporated into the functional circuitry of the brain. These neurogenic zones appear to be vestiges of the original developmental program that initiates brain formation. The largest of these germinal regions in the adult brain is the subventricular zone (SVZ), which lines the lateral walls of the lateral ventricles. Neural stem cells produce neuroblasts that migrate from the SVZ along a discrete pathway, the rostral migratory stream, into the olfactory bulb where they form mature neurons involved in the sense of smell. The subgranular layer (SGL) of the hippocampal dentate gyrus is another neurogenic region; new SGL neurons migrate only a short distance and differentiate into hippocampal granule cells. Here, we discuss the surprising finding of neural stem cells in the adult brain and the molecular mechanisms that regulate adult neurogenesis.

Figure 1

(a) Head of a mouse showing the location of the brain and the rostral migratory stream, RMS, (in red) along which newly generated neuroblasts migrate from the SVZ of the lateral ventricle into the olfactory bulb (OB). (b) The migration of newly generated neuroblasts begins at the lateral ventricle, continues along the RMS and terminated in the OB, where mature interneuron populations are generated. (c) Schematic based on electron microscopy showing the cytoarchitecture of the SVZ along the ventricle. Ependymal cells (gray) form a monolayer along the ventricle with astrocytes (green), neuroblasts (red) and transitory amplifying progenitors (TAP) (purple) comprising the SVZ. (d) Schematic showing the migration of neuroblasts along the RMS. Astrocytes (green) ensheath the migrating neuroblasts (red) and are thought to restrict and contain the neuroblasts to their specific pathway. (e) Migrating neuroblasts enter the OB, migrate radially and give rise to granule or periglomerular cells.

Figure 2

(a) Hormonal regulation of neurogenesis in the mammalian brain. Subgranular layer, SGL; subventricular zone, SVZ; lateral ventricle, LV. (b) Current view of the regulation of adult neurogenesis.