Long-range GABAergic inputs regulate neural stem cell quiescence and control adult hippocampal neurogenesis
Open accessAbstract
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.
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Long-range GABAergic projections to PV+ interneurons, at least in the DG, may lead to excitation rather than hyperpolarization of these neurons.
“Moreover, recent work suggests that long-range GABAergic projections to PV+ interneurons, at least in the DG, might lead to the excitation, rather than hyperpolarization, of these neurons [89].”
From An emerging circuit pharmacology of GABAA receptors (2018) · cites this paper as [89]
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References 62 · Cited by 151
- Authors
- Bao, H., Asrican, B., Li, W., Gu, B., Wen, Z., Lim, S.-A., Haniff, I., Ramakrishnan, C., Deisseroth, K., Philpot, B., & Song, J.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Shanghai Jiao Tong University (CN)
- Emory University (US)
- Stanford University (US)
- Corresponding author
- Song, Juan
- ORCID
- Venue
- Cell stem cell
- Publisher
- Elsevier BV
- Published
- 2017-11
- Volume
- 21
- Issue
- 5
- Pages
- 604-617.e5
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC5689456
- OpenAlex
- W2765123285
- Cited by
- 151
- References
- 62
- Citations by year
- 2026: 10 · 2025: 12 · 2024: 12 · 2023: 19 · 2022: 18 · 2021: 22 · 2020: 23 · 2019: 19 · 2018: 14 · 2017: 1 · 2014: 1
- FWCI
- 6.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- NARSAD
- American Heart Association (14SDG20440029)
- Whitehall Foundation
- NIH (R01MH111773, R21MH106939)
- National Major Scientific Instruments Development Project (2012YQ03026007)
- National Nature Science Foundation of China (81421061)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- hippocampal neurogenesis, parvalbumin interneurons, dentate gyrus, medial septum, GABAergic projection neurons, GABA signaling, neurogenic niche
- MeSH terms
- Aging, Animals, Cell Cycle, gamma-Aminobutyric Acid, Hippocampus, Interneurons, Parvalbumins, Septal Nuclei, Gene Deletion, Dentate Gyrus, Mice, Neurogenesis, Neural Stem Cells, GABAergic Neurons
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