Neuroscience. 2nd edition.
Generation of Neurons in the Adult Brain
It has long been known that mature, differentiated neurons do not divide (see Chapter 22). It does not follow, however, that all the neurons that make up the adult brain are produced during embryonic development, even though this interpretation has generally been assumed. The merits of this assumption were questioned in the 1980s, when Fernando Nottebohm and colleagues at Rockefeller University demonstrated the production of new neurons in the brains of adult songbirds. They showed that labeled DNA precursors injected into adult birds could be found subsequently in fully differentiated neurons, indicating that the neurons had undergone their final round of cell division after the labeled precursor was injected. Moreover, the new neurons were able to extend dendrites and project long axons to establish appropriate connections with other brain nuclei. Production of new neurons was apparent in many parts of the birds’ brains, but was especially prominent in areas involved in song production (see Box B in Chapter 24). These observations showed that the adult brain can generate at least some new nerve cells and incorporate them into neural circuits (see also Chapter 15).
The production of new neurons in the adult brain has now been examined in mice, rats, monkeys and, finally, humans. In all cases, however, the new nerve cells in the mammalian CNS have been restricted to just two regions of the brain: (1) The granule cell layer of the olfactory bulb; and (2) the dentate gyrus of the hippocampus. Furthermore, the new nerve cells are primarily local circuit neurons or interneurons. New neurons with long distance projections have not been seen. Each of these populations in the olfactory bulb and hippocampus is apparently generated from nearby sites near the surface of the lateral ventricle. As in bird brains, the newborn nerve cells extend axons and dendrites and become integrated into functional synaptic circuits. Evidently, a limited production of new neurons occurs continually in a few specific loci.
If neurons cannot divide (see Chapter 22), how does the adult brain generate these nerve cells? The answer emerged with the discovery that the sub-ventricular zone that produces neurons during development retains some neural stem cells in the adult. The term “stem cells” refers to a population of cells that are self-renewing—each cell can divide symmetrically to give rise to more cells like itself, but also can divide asymmetrically, giving rise to a new stem cell plus one or more differentiated cells. Over the past decade, several research groups have isolated stem cells from the adult brain that can reproduce in large numbers in cell culture. Such cells can then be induced to differentiate into neurons and glial cells, when exposed to appropriate signals. Many of these same signals mediate neuronal differentiation in normal development. Adult stem cells can be isolated not only from the anterior subventricular zone (near the olfactory bulb) and dentate gyrus, but from many other parts of the forebrain, cerebellum, midbrain, and spinal cord, although they do not apparently produce any new neurons in these sites. Inhibitory signals in these regions may prevent stem cells from generating neurons.
Why the generation of neurons is so limited in the adult brain is not known. This peculiar limitation is presumably related to the reasons discussed in Box D. Nevertheless, the fact that new neurons can be generated in a few regions of the adult brain suggests that this phenomenon can occur throughout the adult CNS. The ability of newly generated neurons to integrate into at least some synaptic circuits adds to the mechanisms available for plasticity in the adult brain. Thus, many investigators have begun to explore the potential applications of stem cell technology for the repair of circuits damaged by traumatic injury or degenerative disease.
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