The subventricular zone (SVZ) of many adult non-human mammals generates large numbers of new neurons destined for the olfactory bulb (OB)1–6. Along the walls of the lateral ventricles, immature neuronal progeny migrate in tangentially-oriented chains that coalesce into a rostral migratory stream (RMS) connecting the SVZ to the OB. The adult human SVZ, in contrast, contains a hypocellular gap layer separating the ependymal lining from a periventricular ribbon of astrocytes7. Some of these SVZ astrocytes can function as neural stem cells in vitro, but their function in vivo remains controversial. An initial report finds few SVZ proliferating cells and rare migrating immature neurons in the RMS of adult humans7. In contrast, a subsequent study indicates robust proliferation and migration in the human SVZ and RMS8,9. Here, we find that the infant human SVZ and RMS contain an extensive corridor of migrating immature neurons before 18 months of age, but, contrary to previous reports8, this germinal activity subsides in older children and is nearly extinct by adulthood. Surprisingly, during this limited window of neurogenesis, not all new neurons in the human SVZ are destined for the OB – we describe a major migratory pathway that targets the prefrontal cortex in humans. Together, these findings reveal robust streams of tangentially migrating immature neurons in human early postnatal SVZ and cortex. These pathways represent potential targets of neurological injuries affecting neonates.
The discovery of neural stem cells in the adult mammalian brain shattered the long-standing belief that neurogenesis is restricted to embryonic and early postnatal periods. The largest germinal region in the adult mammalian brain is the SVZ. The SVZ is classically described as a thin layer of proliferative cells lining the lateral wall of the lateral ventricle (LV) and separated from the ventricular lumen by a layer of ependymal cells (Smart and Leblond 1961;Altman 1969). The existence of NSCs in this region was first suggested by in vitro experiments in which SVZ cells were shown to self-renew and produce neurons, astrocytes, and oligodendrocytes (Reynolds and Weiss 1992;Morshead et al. 1994). In vivo, NSCs generate a large number of young neurons that migrate along the RMS to the OB where they replace multiple types of interneurons (Luskin 1993;Lois and Alvarez-Buylla 1994). NSCs in the SVZ also generate both parenchymal oligodendrocyte progenitors (OPCs) and myelinating oligodendrocytes, most of which migrate into the neighboring corpus callosum (Nait-Oumesmar et al. 1999;Picard-Riera et al. 2002;Menn et al. 2006).Adult neurogenesis leads to the generation and replacement of specific types of neurons in restricted brain regions, including the OB and dentate gyrus of the hippocampus. Many processes of embryonic development are recapitulated during adult neurogenesis, such as neuronal differentiation, migration, maturation, and cell death. However, adult-born neurons confront an environment very different from those born in the developing brain. Adult-born neurons migrate through more complex and frequently extensive territories and must integrate into circuits that are already fully functional. Young neurons in the SVZ and RMS migrate along each other, forming long aggregates of cells called chains (Lois et al. 1996) and are able to migrate long distances in relatively short periods of time (Wichterle et al. 1997). Within 2-5 days from their time of birth in the SVZ, the majority of these young neurons have reached the OB. Once in the OB, young neurons move radially away from the RMS and begin their final differentiation and maturation, a process that takes 5-10 days (Petreanu and Alvarez-Buylla 2002). During this period, new neurons develop dendritic trees and synaptic spines and become functionally integrated into the OB circuitry (Carleton et al. 2003).Initial studies in the neonatal rat brain suggested that new OB neurons originate from a restricted territory in the anterior SVZ, in a region close to the RMS (Luskin 1993; Lois and Alvarez-Buylla 1994). However, subsequent work uncovered an extensive network of chains of young neurons throughout most of the SVZ on the lateral wall of the LV (Doetsch and Alvarez-Buylla 1996), suggesting that migrating cells originate along the length of the lateral ventricular wall. Below, we review new experiments that suggest that the neurogenic SVZ covers regions of the lateral ventricular walls facing the pallium, subpallium, and septum, as well as the RMS. Furthermore, ...
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