Mossy Cells Control Adult Neural Stem Cell Quiescence and Maintenance through a Dynamic Balance between Direct and Indirect Pathways

Neuron. 2018 Aug 8;99(3):493-510.e4. doi: 10.1016/j.neuron.2018.07.010. Epub 2018 Jul 26.

Abstract

Mossy cells (MCs) represent a major population of excitatory neurons in the adult dentate gyrus, a brain region where new neurons are generated from radial neural stem cells (rNSCs) throughout life. Little is known about the role of MCs in regulating rNSCs. Here we demonstrate that MC commissural projections structurally and functionally interact with rNSCs through both the direct glutamatergic MC-rNSC pathway and the indirect GABAergic MC-local interneuron-rNSC pathway. Specifically, moderate MC activation increases rNSC quiescence through the dominant indirect pathway, while high MC activation increases rNSC activation through the dominant direct pathway. In contrast, MC inhibition or ablation leads to a transient increase of rNSC activation, but rNSC depletion only occurs after chronic ablation of MCs. Together, our study identifies MCs as a critical stem cell niche component that dynamically controls adult NSC quiescence and maintenance under various MC activity states through a balance of direct glutamatergic and indirect GABAergic signaling onto rNSCs.

Keywords: adult hippocampal neurogenesis; maintenance; mossy cells; neural stem cells; quiescence.

Publication types

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

MeSH terms

  • Age Factors
  • Animals
  • Female
  • Male
  • Membrane Potentials / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mossy Fibers, Hippocampal / physiology*
  • Neural Stem Cells / physiology*
  • Neurogenesis / physiology*
  • Random Allocation
  • Signal Transduction / physiology*