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letters to nature.................................................................Functional neurogenesisin the adult hippocampusHenriette van Praag*, Alejandro F. Schinder*, Brian R. Christie*,
Nicolas Toni*, Theo D. Palmer* & Fred H. Gage** Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla,California 92037, USA
These authors contributed equally to this work..............................................................................................................................................There is extensive evidence indicating that new neurons are
generated in the dentate gyrus of the adult mammalian hippocampus, a region of the brain that is important for learning and
memory15. However, it is not known whether these new neurons
become functional, as the methods used to study adult neurogenesis are limited to xed tissue. We use here a retroviral vector
expressing green uorescent protein that only labels dividing
cells, and that can be visualized in live hippocampal slices. We
report that newly generated cells in the adult mouse hippocampus
have neuronal morphology and can display passive membrane
properties, action potentials and functional synaptic inputs similar to those found in mature dentate granule cells. Our ndings
demonstrate that newly generated cells mature into functional
neurons in the adult mammalian brain.Hippocampal neurogenesis has been observed in adult animals
from birds to humans16. The newly generated cells may have a
function in cognition and brain repair. For example, manipulations
that increase neurogenesis, such as an enriched environment7 and
exercise8, are associated with improved memory function and
enhanced synaptic plasticity9. In addition, new neurons are generated in the hippocampus after stroke10 and seizures11, and in the
cortex after a selective lesion12, suggesting that they may be involved
in recovery from injury. Stress, on the other hand, has been related
to decreased cell proliferation and memory impairment13,14. However, the conclusions from all of these studies are based on correlations. It is still unclear whether newly generated cells that express
neuronal markers become functional neurons.Embryonic hippocampal progenitors can develop neuronal electrophysiological properties and are able to form functional synapses
in culture15. Furthermore, adult hippocampal progenitors display
voltage-dependent currents in vitro16,17. It remains unknown
whether newly generated cells become functional neurons in vivo,
mainly owing to the methods currently available to study neurogenesis. Both tritiated thymidine1,2,6 and 5-bromodeoxyuridine
(BrdU)35,79 are used to label dividing cells in the adult brain;
however, both methods require processing of the tissue and only
label the soma. To overcome these limitations, we used...