High Plasticity of New Granule Cells in the Aging Hippocampus

Cell Rep. 2017 Oct 31;21(5):1129-1139. doi: 10.1016/j.celrep.2017.09.064.


During aging, the brain undergoes changes that impair cognitive capacity and circuit plasticity, including a marked decrease in production of adult-born hippocampal neurons. It is unclear whether development and integration of those new neurons are also affected by age. Here, we show that adult-born granule cells (GCs) in aging mice are scarce and exhibit slow development, but they display a remarkable potential for structural plasticity. Retrovirally labeled 3-week-old GCs in middle-aged mice were small, underdeveloped, and disconnected. Neuronal development and integration were accelerated by voluntary exercise or environmental enrichment. Similar effects were observed via knockdown of Lrig1, an endogenous negative modulator of neurotrophin receptors. Consistently, blocking neurotrophin signaling by Lrig1 overexpression abolished the positive effects of exercise. These results demonstrate an unparalleled degree of plasticity in the aging brain mediated by neurotrophins, whereby new GCs remain immature until becoming rapidly recruited to the network by activity.

Keywords: adult neurogenesis; dentate gyrus; exercise; functional integration; neurotrophins; synaptogenesis.

MeSH terms

  • Aging*
  • Animals
  • Calbindins / metabolism
  • DNA-Binding Proteins
  • Dendrites / physiology
  • Dentate Gyrus / metabolism
  • Female
  • Hippocampus / metabolism*
  • In Vitro Techniques
  • Membrane Glycoproteins / antagonists & inhibitors
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Confocal
  • Nerve Growth Factors / metabolism
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neuronal Plasticity / physiology*
  • Neurons / physiology
  • Nuclear Proteins / metabolism
  • Patch-Clamp Techniques
  • Physical Conditioning, Animal
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Signal Transduction


  • Calbindins
  • DNA-Binding Proteins
  • Lrig1 protein, mouse
  • Membrane Glycoproteins
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • NeuN protein, mouse
  • Nuclear Proteins
  • RNA, Small Interfering