@article{1c5f996df5a14671a7476784677a2fe3,
title = "Long-Range GABAergic Inputs Regulate Neural Stem Cell Quiescence and Control Adult Hippocampal Neurogenesis",
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.",
keywords = "adult hippocampal neurogenesis, long-range GABA circuit, neural stem cells",
author = "Hechen Bao and Brent Asrican and Weidong Li and Bin Gu and Zhexing Wen and Lim, {Szu Aun} and Issac Haniff and Charu Ramakrishnan and Karl Deisseroth and Benjamin Philpot and Juan Song",
note = "Funding Information: We thank Dr. Bryan Roth, Dr. Garret Stuber, and members of the Song lab for comments and discussions; Dr. Jenny Hsieh from Southwestern Medical Center for retrovirus; and Dipendra Aryal from the Roth lab for technical support of CNO local infusion. This work was supported by grants awarded to J.S. from NARSAD, American Heart Association (14SDG20440029), Whitehall Foundation, and NIH (R01MH111773 and R21MH106939). H.B. was partially supported by National Major Scientific Instruments Development Project (2012YQ03026007) and National Nature Science Foundation of China (81421061). Funding Information: J.S. led the project, designed and supervised experiments, and wrote the manuscript; H.B. designed experiments and 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.-A.L. and I.H. assisted with experiments; and C.R. and K.D. provided Flp-dependent AAV-hM3Dq. Funding Information: We thank Dr. Bryan Roth, Dr. Garret Stuber, and members of the Song lab for comments and discussions; Dr. Jenny Hsieh from Southwestern Medical Center for retrovirus; and Dipendra Aryal from the Roth lab for technical support of CNO local infusion. This work was supported by grants awarded to J.S. from NARSAD , American Heart Association ( 14SDG20440029 ), Whitehall Foundation , and NIH ( R01MH111773 and R21MH106939 ). H.B. was partially supported by National Major Scientific Instruments Development Project ( 2012YQ03026007 ) and National Nature Science Foundation of China ( 81421061 ). Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",
year = "2017",
month = nov,
day = "2",
doi = "10.1016/j.stem.2017.10.003",
language = "English (US)",
volume = "21",
pages = "604--617.e5",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "5",
}