Activity regulates cell death within cortical interneurons through a Calcineurin-dependent mechanism
Open accessAbstract
We demonstrate that cortical interneurons derived from ventral eminences, including the caudal ganglionic eminence, undergo programmed cell death. Moreover, with the exception of VIP interneurons, this occurs in a manner that is activity-dependent. In addition, we demonstrate that, within interneurons, Calcineurin, a calcium-dependent protein phosphatase, plays a critical role in sequentially linking activity to maturation (E15-P5) and survival (P5-P20). Specifically, embryonic inactivation of Calcineurin results in a failure of interneurons to morphologically mature and prevents them from undergoing apoptosis. By contrast, early postnatal inactivation of Calcineurin increases apoptosis. We conclude that Calcineurin serves a dual role of promoting first the differentiation of interneurons and, subsequently, their survival.
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Programmed cell death appears to affect all classes of interneurons.
“This process seems to impact all classes of interneurons (Denaxa et al., 2018; Priya et al., 2018; Wong et al., 2018) (Figure 6A).”
From Development and Functional Diversification of Cortical Interneurons (2018) · cites this paper as Priya et al., 2018
Decreasing interneuron excitability by overexpressing Kir2.1 cell-autonomously reduces survival.
“while decreasing the excitability of interneurons through the overexpression of the inward-rectifying potassium channel Kir2.1 cell-autonomously diminishes their survival (Close et al., 2012; Priya et al., 2018) (Figure 6B).”
From Development and Functional Diversification of Cortical Interneurons (2018) · cites this paper as Priya et al., 2018
Cell-autonomous manipulation of cortical interneuron excitability influences their survival.
“Second, cell-autonomous manipulation of the excitability of cortical interneurons influence their survival.”
From Development and Functional Diversification of Cortical Interneurons (2018) · cites this paper as Priya et al., 2018
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References 87 · Cited by 127
Research works printed but not linked: 2
- Levi-Montalcini R 1987 The nerve growth factor 35years later Science 237 1154 1162 3306916
- Sík A Hájos N Gulácsi A Mody I Freund TF 1998 The absence of a major Ca2+ signaling pathway in GABAergic neurons of the hippocampus Proc Natl Acad Sci USA 95 3245 3250 9501248 PMC19727
- Authors
- Priya, R., Paredes, M. F., Karayannis, T., Yusuf, N., Liu, X., Jaglin, X., Graef, I., Alvarez-Buylla, A., & Fishell, G.
- Affiliations
- New York University (US)
- University of California, San Francisco (US)
- Harvard University (US)
- Stanford Medicine (US)
- Broad Institute (US)
- Corresponding author
- Fishell, Gord
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2018-02
- Volume
- 22
- Issue
- 7
- Pages
- 1695-1709
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC6215776
- OpenAlex
- W2787269337
- Cited by
- 127
- References
- 87
- Citations by year
- 2026: 14 · 2025: 13 · 2024: 17 · 2023: 17 · 2022: 14 · 2021: 19 · 2020: 19 · 2019: 8 · 2018: 6
- FWCI
- 4.73
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by-nc-nd)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- National Institutes of Health (R01-NS081297, R01-MH071679, P01-NS074972)
- Simons Foundation (K08NS091537-01A1, R01-EY025174, 274578)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- cortical interneurons, calcineurin, apoptosis, interneuron maturation, caudal ganglionic eminence, VIP interneurons, interneuron differentiation
- MeSH terms
- Animals, Calcium, Cell Count, Cell Survival, Cerebral Cortex, Embryo, Mammalian, Interneurons, Median Eminence, Neuroglia, Solubility, Time Factors, Signal Transduction, Cell Death, Calcineurin, bcl-2-Associated X Protein, Mice
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