Nicotinic α7 Receptor Clusters on Hippocampal GABAergic Neurons: Regulation by Synaptic Activity and Neurotrophins
Open accessAbstract
Nicotinic acetylcholine receptors containing the alpha7 gene product are expressed at substantial levels in the hippocampus. Because of their specific locations and their high relative calcium permeability, the receptors not only mediate cholinergic transmission in the hippocampus but also influence signaling at noncholinergic synapses. We have used fluorescently labeled alpha-bungarotoxin to image alpha7-containing receptors on hippocampal neurons and to examine their regulation in culture. The highest levels of staining for such receptors were most commonly found on GABAergic interneurons identified immunohistochemically. The receptors were distributed in clusters on the soma and dendrites and were localized in part at GABAergic synapses. A 3 d blockade of electrical activity with tetrodotoxin or NMDA receptors with APV dramatically reduced the proportion of GABAergic neurons expressing high levels of receptor staining and reduced the mean number of distinguishable receptor clusters on individual neurons. Blockade of either GABA(A) receptors with bicuculline or nicotinic receptors with d-tubocurarine had no effect, although exposure to nicotine could increase the level of receptor staining. Anti-BDNF and anti-NGF antibodies produced decrements equivalent to those of tetrodotoxin and APV, whereas addition of BDNF and NGF each increased staining levels and increased the number of distinguishable receptor clusters on GABAergic neurons. The exogenous neurotrophins could not, however, overcome the effects of either tetrodotoxin or APV. The results indicate that both NMDA receptor activation and the neurotrophins BDNF and NGF are necessary to sustain the distribution patterns of alpha7-containing nicotinic receptors on GABAergic hippocampal neurons.
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Nicotinic acetylcholine receptors contribute to the maturation of GABAergic and glutamatergic synapses.
“Recent studies have also shown that nAChRs contribute to the maturation of GABAergic (Kawai et al., 2002; Zago et al., 2006) and glutamatergic (Lozada et al., 2012a, b) synapses, highlighting an important role for ACh signaling in synaptic development, as well as neuronal pathfinding and target selection (reviewed in (Role and Berg, 1996).”
From Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior (2012) · cites this paper as Kawai et al., 2002
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Self-citation
- Authors
- Kawai, H., Zago, W., & Berg, D. K.
- Affiliations
- University of California San Diego (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2002-09-15
- Volume
- 22
- Issue
- 18
- Pages
- 7903-7912
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6758091
- OpenAlex
- W2101234460
- Cited by
- 140
- References
- 55
- Citations by year
- 2025: 1 · 2024: 3 · 2022: 1 · 2021: 5 · 2020: 3 · 2019: 2 · 2017: 2 · 2016: 4 · 2015: 9 · 2014: 4 · 2013: 10 · 2012: 7
- FWCI
- 3.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- Tobacco-Related Disease Research Program (9RT-0221)
- National Institutes of Health (NS12601)
- National Institute of Neurological Disorders and Stroke (NS12601, NS35469, R01NS012601, R01NS035469)
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- nicotinic acetylcholine receptors, alpha7 nicotinic acetylcholine receptor, hippocampus, GABAergic interneurons, receptor clustering, synaptic activity, NMDA receptor blockade, tetrodotoxin, brain-derived neurotrophic factor, nerve growth factor, neurotrophins, nicotine, calcium permeability
- MeSH terms
- Animals, Cells, Cultured, Fluorescent Dyes, gamma-Aminobutyric Acid, Glutamate Decarboxylase, Hippocampus, Image Processing, Computer-Assisted, Microscopy, Fluorescence, Nerve Growth Factors, Synaptic Transmission, Neurons, Pseudopodia, Receptor Aggregation, Receptors, Nicotinic, Synapses, Tetrodotoxin, Rats, Sprague-Dawley, Presynaptic Terminals, Excitatory Amino Acid Antagonists, GABA Antagonists, Rats, alpha7 Nicotinic Acetylcholine Receptor
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