Oxford University Press, Neurosurgery, 4(58), p. N7, 2006
DOI: 10.1227/01.neu.0000310253.57635.0a
Nature Research, Nature, 7076(439), p. 589-593, 2005
DOI: 10.1038/nature04404
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Adult neurogenesis, the birth and integration of new neurons from adult neural stem cells, represents a striking form of structural plasticity and regenerative capacity of the adult mammalian brain, including humans1–8. Accumulating evidence suggests that neuronal activity regulates adult neurogenesis and new neurons contribute to specific brain functions1–8. The mechanism that regulates the integration of newly generated neurons into the pre-existing functional circuitry in the adult brain is unknown. Here we show that newborn granule cells in the dentate gyrus of the adult hippocampus are tonically activated by ambient γ-aminobutyric acid (GABA) before they are sequentially innervated by GABAergic and glutamatergic synaptic inputs. GABA, the major inhibitory neurotransmitter in the adult brain, initially exerts an excitatory action on newborn neurons due to their high cytoplasmic chloride content9–12. Conversion of GABA-induced depolarisation/excitation into hyperpolarisation/inhibition in newborn neurons leads to significant defects in their synapse formation and dendritic development in vivo. Our study reveals an essential role of GABA in the synaptic integration of newly generated neurons in the adult brain and suggests an unexpected mechanism for activity-dependent regulation of adult neurogenesis where newborn neurons may sense neuronal network activity through tonic and phasic GABA activation.