New neurons continue to be generated in the subgranular zone of the dentate gyrus of the adult mammalian hippocampus1,2,3,4,5. This process has been linked to learning and memory, stress and exercise, and is thought to be altered in neurological disease6,7,8,9,10. In humans, some studies have suggested that hundreds of new neurons are added to the adult dentate gyrus every day11, whereas other studies find many fewer putative new neurons12,13,14. Despite these discrepancies, it is generally believed that the adult human hippocampus continues to generate new neurons. Here we show that a defined population of progenitor cells does not coalesce in the subgranular zone during human fetal or postnatal development. We also find that the number of proliferating progenitors and young neurons in the dentate gyrus declines sharply during the first year of life and only a few isolated young neurons are observed by 7 and 13 years of age. In adult patients with epilepsy and healthy adults (18–77 years; n = 17 post-mortem samples from controls; n = 12 surgical resection samples from patients with epilepsy), young neurons were not detected in the dentate gyrus. In the monkey (Macaca mulatta) hippocampus, proliferation of neurons in the subgranular zone was found in early postnatal life, but this diminished during juvenile development as neurogenesis decreased. We conclude that recruitment of young neurons to the primate hippocampus decreases rapidly during the first years of life, and that neurogenesis in the dentate gyrus does not continue, or is extremely rare, in adult humans. The early decline in hippocampal neurogenesis raises questions about how the function of the dentate gyrus differs between humans and other species in which adult hippocampal neurogenesis is preserved.

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We thank the families who donated the tissue samples used in this study, and J. Rodriguez, V. Tang, J. Cotter and C. Guinto for technical support. S.F.S. was supported by F32 MH103003 and M.F.P. was supported by K08 NS091537. A.A.-B. was supported by NIH grants P01 NS083513, R01 NS028478 and a gift from the John G. Bowes Research Fund. He is the Heather and Melanie Muss Endowed Chair and Professor of Neurological Surgery at UCSF and is a co-founder and serves on the scientific advisory board of Neurona Therapeutics. G.W.M. was partly supported by the Davies/Crandall Endowed Chair For Epilepsy Research at UCLA. G.W.M. and J.C. were supported by NIH NINDS (NS083823 and U01 MH108898). M.C.O. was supported by a Scholar Award from the UCSF Weill Institute for Neurosciences. We acknowledge NSFC grants to Z.Y. (31425011, 31630032, and 31421091). S.M. was supported by fellowships from the European Molecular Biology Organization (EMBO Long-Term Fellowship, ALTF_393-2015) and the German Research Foundation (DFG, MA 7374/1-1). J.M.G.-V. and A.C.-S. were supported by MINECO/FEDER Grant BFU2015-64207-P, Red de Terapia Celular TerCel, Instituto de Salud Carlos III (ISCIII2012-RED-19-016 and RD12/0019/0028) and PROMETEOII/2014/075.

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  1. Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, California 94143, USA

    • Shawn F. Sorrells
    • , Mercedes F. Paredes
    • , Kadellyn Sandoval
    • , Kevin W. Kelley
    • , David James
    • , Simone Mayer
    • , Arnold R. Kriegstein
    • , Michael C. Oldham
    •  & Arturo Alvarez-Buylla
  2. Department of Neurological Surgery, University of California San Francisco, San Francisco, California 94143, USA

    • Shawn F. Sorrells
    • , Kurtis I. Auguste
    • , Edward F. Chang
    • , Michael C. Oldham
    •  & Arturo Alvarez-Buylla
  3. Department of Neurology, University of California San Francisco, San Francisco, California 94143, USA

    • Mercedes F. Paredes
    • , Kadellyn Sandoval
    • , Simone Mayer
    •  & Arnold R. Kriegstein
  4. Laboratorio de Neurobiología Comparada, Instituto Cavanilles, Universidad de Valencia, CIBERNED, Valencia, 46980, Spain

    • Arantxa Cebrian-Silla
    •  & Jose Manuel Garcia-Verdugo
  5. State Key Laboratory of Medical Neurobiology and Institutes of Brain Science, Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China

    • Dashi Qi
    •  & Zhengang Yang
  6. David Geffen School of Medicine, Department of Neurosurgery, Intellectual Development and Disabilities Research Center, University of California Los Angeles, Los Angeles, California 90095, USA

    • Julia Chang
  7. Unidad de Cirugía de la Epilepsia, Hospital Universitario La Fe, Valencia 46026, Spain

    • Antonio J. Gutierrez
  8. Department of Neurosurgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, USA

    • Gary W. Mathern
  9. Department of Psychiatry and Biobehavioral Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, USA

    • Gary W. Mathern
  10. Department of Pathology, University of California San Francisco, San Francisco, California 94143, USA

    • Eric J. Huang


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M.F.P. and S.F.S. contributed equally as co-first authors and A.C.-S., K.S. and D.Q. contributed equally as second authors. Z.Y., A.A.-B., M.F.P. and S.F.S. conceived the study. A.A.-B., S.F.S. and M.F.P. designed and interpreted the experiments and, with A.C.-S., K.S., D.Q., S.M. and D.J., conducted the experiments. K.I.A., E.F.C., J.C., E.J.H., A.J.G., A.R.K. and G.W.M. assisted with specimen collection and conducted clinical and neuropathological reviews. K.W.K. and M.C.O. designed and performed the bioinformatic analyses. A.C.-S. and J.M.G.-V. conducted and interpreted the ultrastructural studies. S.F.S., M.F.P., A.C.-S. and K.S. prepared the figures. A.A.-B., S.F.S. and M.F.P. wrote the manuscript with input from all authors.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Jose Manuel Garcia-Verdugo or Zhengang Yang or Arturo Alvarez-Buylla.

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    This file contains Supplementary Tables 1-4, a Supplementary Discussion and Supplementary References.

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  1. 1.

    3D rendering of the dorsal hippocampus at 14 GW

    The developing dentate gyrus (blue), CA region (orange), dentate neuroepithelium (yellow) are shown and each coloured dot represents the presence of Ki67+ (green), SOX2+ (red) and PAX6+ (white) cells.

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