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Author Notes:

Correspondence to: Juan Song, Ph.D. (juansong@email.unc.edu)

J.S. led the project, designed and supervised experiments, and wrote the manuscript; H.B. designed experiments, performed surgeries, and imaging analysis; B.A. performed electrophysiology recordings; W.L. provided partial financial support for H.B.; B.G. and B.P. performed in vivo EEG recording; Z.W. performed calcium imaging; S.L. and I.H. assisted experiments; C.R. and K.D. provided Flp-dependent AAV-hM3Dq.

We thank Dr. Bryan Roth, Dr. Garret Stuber, and members of Song lab for comments and discussions, Dr. Jenny Hsieh from Southwestern Medical Center for retrovirus, Dipendra Aryal from Roth lab for technical support of CNO local infusion.

Subjects:

Research Funding:

This work was supported by grants awarded to J.S. from NARSAD (Brain and Behavior Research Foundation), American Heart Association, Whitehall Foundation, and NIH (R01MH111773, R21MH106939).

H.B. was partially supported by National Major Scientific Instruments Development Project (2012YQ03026007), and National Nature Science Foundation of China (81421061).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Cell & Tissue Engineering
  • Cell Biology
  • SYNAPTIC INHIBITION
  • CONTAINING NEURONS
  • BRAIN
  • PARVALBUMIN
  • GABA
  • INTERNEURONS
  • CIRCUITRY
  • NETWORK
  • MOUSE
  • DIFFERENTIATION

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

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Journal Title:

Cell Stem Cell

Volume:

Volume 21, Number 5

Publisher:

, Pages 604-+

Type of Work:

Article | Post-print: After Peer 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.

Copyright information:

© 2017 Elsevier Inc.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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