Functional Nicotinic Acetylcholine Receptor Expression in Stem and Progenitor Cells of the Early Embryonic Mouse Cerebral Cortex
Open accessAbstract
The adult cerebral cortex contains nicotinic acetylcholine (ACh) receptors vital to cortical function. However, little is known about the assembly of embryonic nicotinic receptor subunits into functional receptors or whether they play an active role in cortical development. We now report evidence of functional nicotinic acetylcholine receptor channels in fetal mouse cerebral cortex as early as embryonic day 10 (E10), when the cortex consists of dividing stem and progenitor cells. Patch-clamp electrophysiological measurements indicate that nicotine and ACh evoke sizable inward currents characteristic of nicotinic receptors, that are strongly rectifying with a reversal potential near 0 mV. Three different nicotinic agonists, ACh, nicotine, and dimethylphenylpiperazinium, evoked cytosolic Ca(2+) signals. Agonist-evoked Ca(2+) signals and electrophysiological responses were found in greater than 70% of all E10-E11 cells tested and were blocked by nicotinic receptor antagonists. The Ca(2+) response to nicotinic agonists was markedly prolonged in cells from early embryonic stages relative to later stages of development. alpha3, alpha4, and alpha7 receptor subunit proteins were detected immunocytochemically in cortical cells from E10 to birth. The incidence of each subunit declined with embryonic age, suggesting a role in early development. We discuss the possible function of nicotinic receptors in early cortical development and their role as a target for nicotine in the developmental pathologies associated with the fetal tobacco syndrome.
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Even before the cholinergic projections arrive in the cortical areas, the nicotinic and muscarinic receptors are expressed on neural progenitors, playing a role in proliferation/differentiation and axonal guidance events.
“But even before the cholinergic projections arrive in the cortical areas, the nicotinic and muscarinic receptors are expressed on neural progenitors playing a role in proliferation/differentiation and axonal guidance events [214–217].”
From Development of prefrontal cortex (2022) · cites this paper as [215]
The Discussion (page unavailable) reports functional nicotinic receptors on E10 cortical progenitor cells before cholinergic innervation and suggests a possible role in proliferation or differentiation. It does not establish that role, or show muscarinic receptor expression on these progenitors or a role in axonal guidance. (LLM, conf=0.89)
Experimental — accuracy not yet measuredEarly activation or desensitization of nAChRs by nicotine can cause long-term developmental disruption.
“Since nAChRs are functional at early stages of brain development, their early activation and/or desensitization by nicotine can lead to long-term developmental disruption.”
From Developmental toxicity of nicotine: A transdisciplinary synthesis and implications for emerging tobacco products (2017) · cites this paper as [49]
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- Authors
- Atluri, P., Fleck, M. W., Shen, Q., Mah, S. J., Stadfelt, D., Barnes, W., Goderie, S. K., Temple, S., & Schneider, A. S.
- Affiliations
- Albany Medical College (US)
- Corresponding author
- Schneider, A.S.
- ORCID
- Venue
- Developmental Biology
- Publisher
- Elsevier BV
- Published
- 2001-12
- Volume
- 240
- Issue
- 1
- Pages
- 143-156
- ISSN
- 0012-1606 (ISSN-L)
- OpenAlex
- W2080909361
- Cited by
- 110
- References
- 64
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 8 · 2020: 3 · 2019: 7 · 2018: 5 · 2017: 3 · 2016: 4 · 2015: 3 · 2014: 5 · 2013: 4 · 2012: 8
- FWCI
- 1.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r03hd039808-02)
- National Institute of Neurological Disorders and Stroke (R01NS033529)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R03-HD39808)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- nicotinic acetylcholine receptors, embryonic cerebral cortex, cortical development, neural stem cells, progenitor cells, nicotine, acetylcholine, calcium signaling, nicotinic receptor subunits, alpha3 subunit, alpha4 subunit, alpha7 subunit
- MeSH terms
- Acetylcholine, Animals, Calcium, Cerebral Cortex, Dimethylphenylpiperazinium Iodide, Female, Fluorescent Antibody Technique, Nicotine, Pregnancy, Receptors, Nicotinic, Stem Cells, Patch-Clamp Techniques, Calcium Signaling, Mice
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