Ultrastructural Localization of the α4-Subunit of the Neuronal Acetylcholine Nicotinic Receptor in the Rat Substantia Nigra
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The distribution of the alpha4-subunit of the neuronal nicotinic acetylcholine receptor (nAChR) in the rat brain was examined at light and electron microscopy levels using immunohistochemical staining. In the present study we demonstrate the specificity, in both tissue homogenates and brain sections, of a polyclonal antibody raised against the rat nAChR alpha4-subunit. The characterization of this antibody involved: (1) Western blot analysis of rat brain homogenates and membrane extracts from cells previously transfected with diverse combinations of neuronal nAChR subunits, and (2) immunohistochemistry using transfected cells and rat brain tissue. At the light microscope level, the alpha4-subunit-like-immunoreactivity (LI) was widely distributed in the rat brain and matched the distribution of the alpha4-subunit transcripts observed previously by in situ hybridization. Strong immunohistochemical labeling was detected in the mesencephalic dopaminergic nuclei. The nAChRs in this region are thought to be responsible for the modulation of dopaminergic transmission. The neurotransmitter identity of alpha4-immunolabeled neurons in the substantia nigra pars compacta (SNpc) and the ventral tegmental area was thus assessed by investigating the possible colocalization of the nAChR alpha4-subunit with tyrosine hydroxylase using confocal microscopy. The double labeling experiments unambiguously indicated that the alpha4-subunit-LI is present in dopaminergic neurons. At the electron microscope level, the neurons in the SNpc exhibited alpha4-subunit-LI in association with a minority of postsynaptic densities, suggesting that the alpha4-subunit may be a component of functional nAChRs mediating synaptic transmission between midbrain cholinergic neurons and mesencephalic dopaminergic neurons.
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Nicotinic acetylcholine receptors are not clustered at postsynaptic membranes apposed to sites of acetylcholine release, but are rather dispersed along the surface and intracellular compartments of neurons, including presynaptic terminals, cell bodies and axons.
“nAChRs are not clustered at postsynaptic membranes apposed to sites of ACh release, but are rather dispersed along the surface (and intracellular compartments) of neurons, including presynaptic terminals (McGehee et al., 1995; Vidal and Changeux, 1993), cell bodies and even axons (Arroyo-Jimenez et al., 1999; Hill Jr. et al., 1993; Kawai et al., 2007).”
From Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior (2012) · cites this paper as Arroyo-Jimenez et al., 1999
There is an anatomical mismatch between the sites of acetylcholine release and the location of cholinergic receptors.
“There is an anatomical mismatch between the sites of ACh release (Houser, 1990; Wainer et al., 1984a; Wainer et al., 1984b) and the location of cholinergic receptors (Arroyo-Jimenez et al., 1999; Hill Jr. et al., 1993; Kawai et al., 2007).”
From Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior (2012) · cites this paper as Arroyo-Jimenez et al., 1999
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Self-citationMaskos, U. (2008) · British Journal of Pharmacology · doi:10.1038/bjp.2008.5 · Cited by 139 · see citing works
Identification of Sequence Motifs That Target Neuronal Nicotinic Receptors to Dendrites and Axons
Xu, J., Zhu, Y., & Heinemann, S. F. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.0840-06.2006 · Cited by 96 · see citing works
Corringer, P.-J., Sallette, J., & Changeux, J.-P. (2006) · Journal of Physiology-Paris · doi:10.1016/j.jphysparis.2005.12.012 · Cited by 86 · see citing works
Commons, K. G. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.02.056 · Cited by 17 · see citing works
Corsini, S., Tortora, M., & Nistri, A. (2016) · The Journal of Physiology · doi:10.1113/jp272591 · Cited by 16 · see citing works
- Authors
- Arroyo-Jiménez, M. D. M., Bourgeois, J.-P., Marubio, L. M., Le Sourd, A.-M., Ottersen, O. P., Rinvik, E., Fairén, A., & Changeux, J.-P.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- University of Oslo (NO)
- Consejo Superior de Investigaciones Científicas (ES)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1999-08-01
- Volume
- 19
- Issue
- 15
- Pages
- 6475-6487
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6782828
- OpenAlex
- W1818352744
- Cited by
- 110
- References
- 91
- Citations by year
- 2025: 2 · 2024: 1 · 2022: 2 · 2020: 1 · 2018: 3 · 2016: 2 · 2015: 3 · 2014: 2 · 2013: 1 · 2012: 2
- FWCI
- 4.13
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- Comunidad de Madrid
- European Commission
- 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
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Keywords
- nicotinic acetylcholine receptors, alpha4 subunit, substantia nigra, dopaminergic neurons, postsynaptic density, tyrosine hydroxylase, ventral tegmental area, antibody specificity, subcellular localization, rat brain
- MeSH terms
- Animals, Brain, Immunohistochemistry, Neurons, Receptors, Nicotinic, Substantia Nigra, Tissue Distribution, Tyrosine 3-Monooxygenase, Rats, Sprague-Dawley, Protein Isoforms, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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