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Acetylcholine Activates an α-Bungarotoxin-Sensitive Nicotinic Current in Rat Hippocampal Interneurons, But Not Pyramidal Cells
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The effects of acetylcholine on both pyramidal neurons and interneurons in the area CA1 of the rat hippocampus were examined, using intracellular recording techniques in an in vitro slice preparation. In current-clamp mode, fast local application of acetylcholine (ACh) to the soma of inhibitory interneurons in stratum radiatum resulted in depolarization and rapid firing of action potentials. Under voltage-clamp, ACh produced fast, rapidly desensitizing inward currents that were insensitive to atropine but that were blocked by nanomolar concentrations of the nicotinic α7 receptor-selective antagonists α-bungarotoxin (αBgTx) and methyllycaconitine. Nicotinic receptor antagonists that are not selective for α7-containing receptors had little (mecamylamine) or no effect (dihydro-β-erythroidine) on the ACh-induced currents. Glutamate receptor antagonists had no effect on the ACh-evoked response, indicating that the current was not mediated by presynaptic facilitation of glutamate release. However, the current could be desensitized almost completely by bath superfusion with 100 n m nicotine. In contrast to those actions on interneurons, application of ACh to the soma of CA1 pyramidal cells did not produce a detectable current. Radioligand-binding experiments with [125 I]-αBgTx demonstrated that stratum radiatum interneurons express α7-containing nAChRs, and in situ hybridization revealed significant amounts of α7 mRNA. CA1 pyramidal cells did not show specific binding of [125 I]-αBgTx and only low levels of α7 mRNA. These results suggest that, in addition to their proposed presynaptic role in modulating transmitter release, α7-containing nAChRs also may play a postsynaptic role in the excitation of hippocampal interneurons. By desensitizing these receptors, nicotine may disrupt this action and indirectly excite pyramidal neurons by reducing GABAergic inhibition.
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“The α7-nicotinic receptor is found presynaptically on glutamate nerve terminals and postsynaptically on inhibitory interneurons (Figure 2B), particularly in the hippocampus and nucleus reticularis thalamis (9).”
From Sensory Processing Dysfunction in the Personal Experience and Neuronal Machinery of Schizophrenia (2015) · cites this paper as [9]
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“For both PPI and P50 gating, despite the origin of the effect in reticular brain stem neurons, the response engages an entire network of brain circuits, the dopaminergic circuits of the basal ganglia for PPI and the basal cholinergic nuclei and cortex for P50 gating (8, 9).”
From Sensory Processing Dysfunction in the Personal Experience and Neuronal Machinery of Schizophrenia (2015) · cites this paper as [9]
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Goswamee, P., & McQuiston, A. R. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00267 · Cited by 13
Synaptic interactions and inhibitory regulation in auditory cortex
Askew, C. E., & Metherate, R. (2015) · Biological Psychology · doi:10.1016/j.biopsycho.2015.11.001 · Cited by 13
Metadata
- Authors
- Frazier, C. J., Rollins, Y. D., Breese, C. R., Leonard, S., Freedman, R., & Dunwiddie, T. V.
- Affiliations
- University of Colorado Health (US)
- United States Department of Veterans Affairs (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1998-02-15
- Volume
- 18
- Issue
- 4
- Pages
- 1187-1195
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6792737
- OpenAlex
- W2112157534
- Cited by
- 374
- References
- 48
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 9 · 2020: 6 · 2019: 6 · 2018: 9 · 2017: 6 · 2016: 8 · 2015: 18 · 2014: 13 · 2013: 10 · 2012: 15
- FWCI
- 10.12
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r29aa011164-05)
- National Institute on Alcohol Abuse and Alcoholism (AA11164)
- National Institute on Aging (R01AG010755)
- National Institute of Mental Health (MH-44212, P50MH044212)
- National Institute on Drug Abuse (DA 03194, R01DA003194, R01DA009457)
- 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 › Ion channel regulation and function
- Keywords
- acetylcholine, alpha7 nicotinic acetylcholine receptor, alpha-bungarotoxin, hippocampal interneurons, CA1 pyramidal neurons, postsynaptic excitation, GABAergic inhibition, stratum radiatum, nicotinic antagonists
- MeSH terms
- Acetylcholine, Animals, Bungarotoxins, Electric Conductivity, gamma-Aminobutyric Acid, Hippocampus, Interneurons, Male, Nicotine, Receptors, Nicotinic, RNA, Messenger, Rats, Sprague-Dawley, Receptors, Presynaptic, Pyramidal Cells, Rats
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