Long-Range GABAergic Inputs Regulate Neural Stem Cell Quiescence and Control Adult Hippocampal Neurogenesis

Hechen Bao, Brent Asrican, Weidong Li, Bin Gu, Zhexing Wen, Szu Aun Lim, Issac Haniff, Charu Ramakrishnan, Karl Deisseroth, Benjamin Philpot, Juan Song

Research output: Contribution to journalArticlepeer-review

Abstract

The quiescence of adult neural stem cells (NSCs) is regulated by local parvalbumin (PV) interneurons within the dentate gyrus (DG). Little is known about how local PV interneurons communicate with distal brain regions to regulate NSCs and hippocampal neurogenesis. Here, we identify GABAergic projection neurons from the medial septum (MS) as the major afferents to dentate PV interneurons. Surprisingly, dentate PV interneurons are depolarized by GABA signaling, which is in sharp contrast to most mature neurons hyperpolarized by GABA. Functionally, these long-range GABAergic inputs are necessary and sufficient to maintain adult NSC quiescence and ablating them leads to NSC activation and subsequent depletion of the NSC pool. Taken together, these findings delineate a GABAergic network involving long-range GABAergic projection neurons and local PV interneurons that couples dynamic brain activity to the neurogenic niche in controlling NSC quiescence and hippocampal neurogenesis. Bao et al. demonstrate that long-range GABAergic projections from the medial septum control adult hippocampal neurogenesis through depolarizing GABA signaling onto local PV interneurons. Functionally, these long-range inputs are required for maintaining NSC quiescence and ablating them depletes the NSC pool and impairs neurogenesis.

Original languageEnglish (US)
Pages (from-to)604-617.e5
JournalCell stem cell
Volume21
Issue number5
DOIs
StatePublished - Nov 2 2017

Keywords

  • adult hippocampal neurogenesis
  • long-range GABA circuit
  • neural stem cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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