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Cell Stem Cell. 2017 Nov 2;21(5):604-617.e5. doi: 10.1016/j.stem.2017.10.003.

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

Author information

1
Bio-X Institutes, Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai 200240, China; Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599, USA.
2
Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599, USA.
3
Bio-X Institutes, Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai 200240, China.
4
Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC 27599, USA.
5
Department of Psychiatry and Behavioral Science, Emory University, Atlanta, GA 30322, USA.
6
Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
7
Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC 27599, USA; Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA.
8
Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599, USA; Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA. Electronic address: juansong@email.unc.edu.

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.

KEYWORDS:

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

Comment in

PMID:
29100013
PMCID:
PMC5689456
DOI:
10.1016/j.stem.2017.10.003
[Indexed for MEDLINE]
Free PMC Article

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