Intrinsically determined cell death of developing cortical interneurons.

The cell death of inhibitory neurons, which originate far from the cortical areas to which they migrate during embryonic development, is determined autonomously rather than by competition for trophic signals from other cell types. It has long been known that apoptosis, a form of programmed cell death, eliminates young cells from developing tissues. In the field of neurobiology, it is widely believed that developmental neuronal-cell death results from cellular competition for environmentally derived survival signals that selects for an optimally sized and properly wired population of neurons. This study of developmental cell death in the mouse cortex in vivo, in vitro and after transplantati…

Extensive migration of young neurons into the infant human frontal lobe

Building the human brain As the brain develops, neurons migrate from zones of proliferation to their final locations, where they begin to build circuits. Paredes et al. have discovered that shortly after birth, a group of neurons that proliferates near the ventricles migrates in chains alongside circulatory vessels into the frontal lobes (see the Perspective by McKenzie and Fishell). Young neurons that migrate postnatally into the anterior cingulate cortex then develop features of inhibitory interneurons. The number of migratory cells decreases over the first 7 months of life, and by 2 years of age, migratory cells are not evident. Any damage during migration, such as hypoxia, may affect th…

Axons take a dive

In the walls of the lateral ventricles of the adult mammalian brain, neural stem cells (NSCs) and ependymal (E1) cells share the apical surface of the ventricular-subventricular zone (V-SVZ). In a recent article, we show that supraependymal serotonergic (5HT) axons originating from the raphe nuclei in mice form an extensive plexus on the walls of the lateral ventricles where they contact E1 cells and NSCs. Here we further characterize the contacts between 5HT supraependymal axons and E1 cells in mice, and show that suprependymal axons tightly associated to E1 cells are also present in the walls of the human lateral ventricles. These observations raise interesting questions about the functio…

Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults.

New neurons continue to be generated in the subgranular zone of the dentate gyrus of the adult mammalian hippocampus(1-5). This process has been linked to learning and memory, stress and exercise, and is thought to be altered in neurological disease(6-10). In humans, some studies have suggested that hundreds of new neurons are added to the adult dentate gyrus every day(11), whereas other studies find many fewer putative new neurons(12-14). Despite these discrepancies, it is generally believed that the adult human hippocampus continues to generate new neurons. Here we show that a defined population of progenitor cells does not coalesce in the subgranular zone during human fetal or postnatal …

Brain size and limits to adult neurogenesis

The walls of the cerebral ventricles in the developing embryo harbor the primary neural stem cells from which most neurons and glia derive. In many vertebrates, neurogenesis continues postnatally and into adulthood in this region. Adult neurogenesis at the ventricle has been most extensively studied in organisms with small brains, such as reptiles, birds, and rodents. In reptiles and birds, these progenitor cells give rise to young neurons that migrate into many regions of the forebrain. Neurogenesis in adult rodents is also relatively widespread along the lateral ventricles, but migration is largely restricted to the rostral migratory stream into the olfactory bulb. Recent work indicates t…

Immature excitatory neurons develop during adolescence in the human amygdala.

The human amygdala grows during childhood, and its abnormal development is linked to mood disorders. The primate amygdala contains a large population of immature neurons in the paralaminar nuclei (PL), suggesting protracted development and possibly neurogenesis. Here we studied human PL development from embryonic stages to adulthood. The PL develops next to the caudal ganglionic eminence, which generates inhibitory interneurons, yet most PL neurons express excitatory markers. In children, most PL cells are immature (DCX+PSA-NCAM+), and during adolescence many transition into mature (TBR1+VGLUT2+) neurons. Immature PL neurons persist into old age, yet local progenitor proliferation sharply d…

Does Adult Neurogenesis Persist in the Human Hippocampus?

Positive Controls in Adults and Children Support That Very Few, If Any, New Neurons Are Born in the Adult Human Hippocampus.

Adult hippocampal neurogenesis was originally discovered in rodents. Subsequent studies identified the adult neural stem cells and found important links between adult neurogenesis and plasticity, behavior, and disease. However, whether new neurons are produced in the human dentate gyrus (DG) during healthy aging is still debated. We and others readily observe proliferating neural progenitors in the infant hippocampus near immature cells expressing doublecortin (DCX), but the number of such cells decreases in children and few, if any, are present in adults. Recent investigations using dual antigen retrieval find many cells stained by DCX antibodies in adult human DG. This has been interprete…