Alpha4 containing nicotinic receptors are positioned to mediate postsynaptic effects on 5-HT neurons in the rat dorsal raphe nucleus
Open accessAbstract
Nicotinic acetylcholine receptors containing the alpha4 and beta2 subunits constitute the most abundant high-affinity binding site of nicotine in the brain and are critical for the addictive qualities of nicotine. 5-HT neurotransmission is thought to be an important contributor to nicotine addiction. Therefore in this study it was examined how alpha4-containing receptors are positioned to modulate the function of 5-HT neurons using ultrastructural analysis of immunolabeling for the alpha4 receptor subunit in the dorsal raphe nucleus (DR), a primary source of forebrain 5-HT in the rat. Of 150 profiles labeled for the alpha4 subunit, 140 or 93% consisted of either soma or dendrites, these were often small-caliber (distal) dendrites <1.5 microm in diameter (63/150 or 42%). The majority (107/150 or 71%) of profiles containing labeling for alpha4 were dually labeled for the synthetic enzyme for 5-HT, tryptophan hydroxylase (TPH). Within dendrites immunogold labeling for alpha4 was present on the plasma membrane or near postsynaptic densities. However, labeling for alpha4 was commonly localized to the cytoplasmic compartment often associated with smooth endoplasmic reticulum, plausibly representing receptors in transit to or from the plasma membrane. Previous studies have suggested that nicotine presynaptically regulates activity onto 5-HT neurons, however alpha4 immunolabeling was detected in only 10 axons in the DR or 7% of profiles sampled. This finding suggest that alpha4 containing receptors are minor contributors to presynaptic regulation of synaptic activity onto 5-HT neurons, but rather alpha4 containing receptors are positioned to influence 5-HT neurons directly at postsynaptic sites.
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Endogenous α4β2 nAChRs localize at least partially to the smooth ER in mouse dorsal raphe and rat cortical neurons.
“Electron microscopy studies in mouse dorsal raphe and rat cortical neurons show that endogenous α4β2 nAChRs localize at least partially to the smooth ER (Hill et al., 1993; Commons, 2008).”
From Nicotine up-regulates α4β2 nicotinic receptors and ER exit sites via stoichiometry-dependent chaperoning (2011) · cites this paper as Commons, 2008
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- Authors
- Commons, K. G.
- Affiliations
- Boston Children's Hospital (US)
- Corresponding author
- Commons, K.G.
- ORCID
- Commons, K.G.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2008-05
- Volume
- 153
- Issue
- 3
- Pages
- 851-859
- ISSN
- 0306-4522 (ISSN-L)
- PMC
- PMC2601689
- OpenAlex
- W2076024553
- Cited by
- 17
- References
- 45
- Citations by year
- 2026: 2 · 2023: 1 · 2021: 1 · 2015: 1 · 2014: 2 · 2013: 3 · 2012: 4
- FWCI
- 0.41
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Drug Abuse (DA‐021801, R01DA021801)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD018655, P30HD-18655)
- 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, dorsal raphe nucleus, serotonergic neurons, postsynaptic modulation, tryptophan hydroxylase, dendrites, postsynaptic density, smooth endoplasmic reticulum, presynaptic modulation, nicotine dependence, ultrastructural localization
- MeSH terms
- Animals, Fluorescent Antibody Technique, Immunohistochemistry, Neurons, Raphe Nuclei, Receptors, Nicotinic, Serotonin, Synaptic Membranes, Microscopy, Electron, Transmission, Rats
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