Activation of local inhibitory circuits in the dentate gyrus by adult-born neurons

Hippocampus. 2016 Jun;26(6):763-78. doi: 10.1002/hipo.22557. Epub 2016 Feb 8.


Robust incorporation of new principal cells into pre-existing circuitry in the adult mammalian brain is unique to the hippocampal dentate gyrus (DG). We asked if adult-born granule cells (GCs) might act to regulate processing within the DG by modulating the substantially more abundant mature GCs. Optogenetic stimulation of a cohort of young adult-born GCs (0 to 7 weeks post-mitosis) revealed that these cells activate local GABAergic interneurons to evoke strong inhibitory input to mature GCs. Natural manipulation of neurogenesis by aging-to decrease it-and housing in an enriched environment-to increase it-strongly affected the levels of inhibition. We also demonstrated that elevating activity in adult-born GCs in awake behaving animals reduced the overall number of mature GCs activated by exploration. These data suggest that inhibitory modulation of mature GCs may be an important function of adult-born hippocampal neurons. © 2015 Wiley Periodicals, Inc.

Keywords: adult neurogenesis; dentate gyrus; granule cells; hippocampus; inhibition; interneurons; optogenetics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / cytology
  • Adult Stem Cells / physiology
  • Animals
  • Cohort Studies
  • Dentate Gyrus / cytology
  • Dentate Gyrus / physiology*
  • Environment
  • Exploratory Behavior / physiology
  • Female
  • Housing, Animal
  • Male
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neural Inhibition / physiology*
  • Neural Pathways / cytology
  • Neural Pathways / physiology
  • Neural Stem Cells / cytology
  • Neural Stem Cells / physiology
  • Neurogenesis / physiology*
  • Neurons / cytology
  • Neurons / physiology*
  • Optogenetics
  • Proto-Oncogene Proteins c-fos / metabolism
  • Synaptic Transmission / physiology
  • gamma-Aminobutyric Acid / metabolism


  • Proto-Oncogene Proteins c-fos
  • gamma-Aminobutyric Acid