Modulating Neuronal Competition Dynamics in the Dentate Gyrus to Rejuvenate Aging Memory Circuits

Neuron. 2016 Sep 21;91(6):1356-1373. doi: 10.1016/j.neuron.2016.08.009. Epub 2016 Sep 1.


The neural circuit mechanisms underlying the integration and functions of adult-born dentate granule cell (DGCs) are poorly understood. Adult-born DGCs are thought to compete with mature DGCs for inputs to integrate. Transient genetic overexpression of a negative regulator of dendritic spines, Kruppel-like factor 9 (Klf9), in mature DGCs enhanced integration of adult-born DGCs and increased NSC activation. Reversal of Klf9 overexpression in mature DGCs restored spines and activity and reset neuronal competition dynamics and NSC activation, leaving the DG modified by a functionally integrated, expanded cohort of age-matched adult-born DGCs. Spine elimination by inducible deletion of Rac1 in mature DGCs increased survival of adult-born DGCs without affecting proliferation or DGC activity. Enhanced integration of adult-born DGCs transiently reorganized adult-born DGC local afferent connectivity and promoted global remapping in the DG. Rejuvenation of the DG by enhancing integration of adult-born DGCs in adulthood, middle age, and aging enhanced memory precision.

MeSH terms

  • Adult Stem Cells / cytology
  • Aging / physiology*
  • Animals
  • Cell Proliferation / genetics
  • Cell Survival / genetics
  • Dendritic Spines / physiology
  • Dentate Gyrus / metabolism
  • Dentate Gyrus / physiology*
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism
  • Kruppel-Like Transcription Factors / physiology
  • Memory / physiology*
  • Mice
  • Mutation
  • Neural Stem Cells / metabolism
  • Neural Stem Cells / physiology
  • Neurogenesis / physiology
  • Neurons / physiology
  • Neuropeptides / genetics
  • Up-Regulation
  • rac1 GTP-Binding Protein / genetics


  • Klf9 protein, mouse
  • Kruppel-Like Transcription Factors
  • Neuropeptides
  • Rac1 protein, mouse
  • rac1 GTP-Binding Protein