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Neurons born in the adult dentate gyrus form functional synapses with target cells

Nature Neuroscience volume 11, pages 901907 (2008) | Download Citation


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Adult neurogenesis occurs in the hippocampus and the olfactory bulb of the mammalian CNS. Recent studies have demonstrated that newborn granule cells of the adult hippocampus are postsynaptic targets of excitatory and inhibitory neurons, but evidence of synapse formation by the axons of these cells is still lacking. By combining retroviral expression of green fluorescent protein in adult-born neurons of the mouse dentate gyrus with immuno-electron microscopy, we found output synapses that were formed by labeled terminals on appropriate target cells in the CA3 area and the hilus. Furthermore, retroviral expression of channelrhodopsin-2 allowed us to light-stimulate newborn granule cells and identify postsynaptic target neurons by whole-cell recordings in acute slices. Our structural and functional evidence indicates that axons of adult-born granule cells establish synapses with hilar interneurons, mossy cells and CA3 pyramidal cells and release glutamate as their main neurotransmitter.

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Change history

  • 20 July 2008

    In the version of this article initially published online, the reference to earlier figures in the legend of Figure 5 is incorrect. For the legend of Figure 5c, the correct sentence should read "...(acquisition was interrupted from 20-25 min; same cell as in Fig. 4a-e)". The error has been corrected for all versions of this article.


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We would like to thank J. Jepsen and N. Nashi for technical assistance, S. Herlitze for providing the ChR2 construct, L. Petreanu for helpful discussions, J. Simon for artwork, J. Fiala for providing software and M.L. Gage for helpful suggestions to improve this manuscript. We also acknowledge the support of the Picower Foundation, Lookout Foundation, McDonnell Foundation, US National Institutes of Health grants NS050217 (to F.H.G.) and NS038331 (to C.E.R.), Agencia Nacional de Promoción Científica, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), and the Howard Hughes Medical Institute (to A.F.S.). D.A.L. and G.L. were supported by fellowships from CONICET.

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Author notes

    • Nicolas Toni
    •  & Diego A Laplagne

    These authors contributed equally to this work.


  1. Laboratory of Genetics, Salk Institute, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.

    • Nicolas Toni
    • , Chunmei Zhao
    •  & Fred H Gage
  2. Laboratory of Neuronal Plasticity, Leloir Institute–CONICET, Av. Patricias Argentinas 435, (1405) Buenos Aires, Argentina.

    • Diego A Laplagne
    • , Gabriela Lombardi
    •  & Alejandro F Schinder
  3. Department of Anatomy & Neurobiology, University of California at Irvine, School of Medicine, Irvine, California 92697-1275, USA.

    • Charles E Ribak


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N.T. contributed to the concept, designed and carried out the structural experiments, analyzed the data, and wrote the manuscript. D.A.L. contributed to the concept, designed and performed the functional experiments, analyzed the data, and wrote the manuscript. C.Z. contributed to the experimental design, provided samples for the structural experiments, carried out and analyzed confocal images of presynaptic terminals, and revised the manuscript. G.L. prepared retroviral stocks, performed immunofluorescence and obtained images of ChR2-positive neurons. C.E.R. contributed to setting up the technique for immuno-electron microscopy of GFP, the analysis of electron micrographs, and the writing and revision of the manuscript. F.H.G. and A.F.S. contributed to the concept, designed the experiments, analyzed the data, wrote the manuscript and provided financial support.

Corresponding authors

Correspondence to Fred H Gage or Alejandro F Schinder.

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