New Neurons in Old Brains Make New Contacts
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Studies over the last few years have debunked the dogma that new neurons cannot grow in adult mammalian brains. In fact, compelling evidence now exists for active neurogenesis in two distinct region of the CNS, the olfactory bulb and the dentate gyrus of the hippocampus. It has been harder to prove, however, if neurons born in adult brains are functional. A letter in today's Nature, from Fred Gage's lab at the Salk Institute, clearly shows that they are.
Gage and colleagues used a retroviral vector to label dividing cells with green fluorescent protein (GFP). The beauty of this technique is that brain slices can be removed, examined microscopically for neurogenesis, and then followed up with electrophysiological measurements. This offers a considerable advantage over previous radioactive labeling methods, which require that the tissue be fixed-i.e. killed-for imaging.
The authors found GFP-expressing cells in mouse brain four weeks after injecting the viral vector into the dentate gyrus. Cells expressing neural markers continued to grow and mature for at least four months, during which time their size, branch points, and number of spines all increased by around sixty percent.
First author van Praag et al. then used electrophysiology to test if the new neurons functioned. For a neuron to become fully integrated into the neural circuitry it must have intact efferent and afferent pathways. The former were tested by measuring their response to direct stimulation; the cells displayed action potentials and firing rates that were almost identical to mature neurons. The latter were confirmed by stimulating the perforant pathway, which is the major input to the granule cell layer of the hippocampus. In this case, the response of mature granule cells and new GFP-expressing cells were almost identical, indicating that the new cells were indeed functionally integrated into the hippocampus. "It will be crucial to determine the functional significance of these newly generated cells in adult brain," the authors write. Are they really needed, and what exactly do they do?—Tom Fagan
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Primary Papers
- van Praag H, Schinder AF, Christie BR, Toni N, Palmer TD, Gage FH. Functional neurogenesis in the adult hippocampus. Nature. 2002 Feb 28;415(6875):1030-4. PubMed.
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This is indeed the first report that newborn neurons in adult brain have morphological and electrophysiological characteristics of adult granule cells, and thereby demonstrates that these new neurons are functional. This represents a major advance by providing the first evidence of the functionality of these newborn cells. However, having said that, and as indicated in the last paragraph of the paper, the significance of these new neurons in the context of the function of the hippocampus or the behavior of the animal remains to be determined. This is a difficult task because it requires selective manipulation of adult neurogenesis, followed by a study of the functional consequences of increased or decreased numbers of new neurons. For example, how does neurogenesis impact behavioral models of learning and memory?
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