Nicotinic excitatory postsynaptic potentials in hippocampal CA1 interneurons are predominantly mediated by nicotinic receptors that contain α4 and β2 subunits
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In the hippocampus, activation of nicotinic receptors that include α4 and β2 subunits (α4β2*) facilitates memory formation. α4β2* receptors may also play a role in nicotine withdrawal, and their loss may contribute to cognitive decline in aging and Alzheimer's disease (AD). However, little is known about their cellular function in the hippocampus. Therefore, using optogenetics, whole cell patch clamping and voltage-sensitive dye (VSD) imaging, we measured nicotinic excitatory postsynaptic potentials (EPSPs) in hippocampal CA1. In a subpopulation of inhibitory interneurons, release of ACh resulted in slow depolarizations (rise time constant 33.2 ± 6.5 ms, decay time constant 138.6 ± 27.2 ms) mediated by the activation of α4β2* nicotinic receptors. These interneurons had somata and dendrites located in the stratum oriens (SO) and stratum lacunosum-moleculare (SLM). Furthermore, α4β2* nicotinic EPSPs were largest in the SLM. Thus, our data suggest that nicotinic EPSPs in hippocampal CA1 interneurons are predominantly mediated by α4β2* nicotinic receptors and their activation may preferentially affect extrahippocampal inputs in SLM of hippocampal CA1.
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Cholinergic signaling is important in the integration of excitatory inputs, specifically via α4β2 nAChRs.
“Recent voltage-sensitive dye imaging (VSDi) studies have demonstrated the importance of cholinergic signaling in the integration of excitatory inputs, specifically via a4b2 nAChRs (Bell et al, 2011; McQuiston, 2010).”
From Divergent Functional Effects of Sazetidine-A and Varenicline During Nicotine Withdrawal (2013) · cites this paper as Bell et al, 2011
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- Authors
- Bell, K. A., Shim, H., Chen, C.-K., & McQuiston, A. R.
- Affiliations
- Virginia Commonwealth University (US)
- Corresponding author
- McQuiston, A. Rory
- ORCID
- Chen, Ching-Kang
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2011-12
- Volume
- 61
- Issue
- 8
- Pages
- 1379-1388
- ISSN
- 0028-3908 (ISSN-L)
- PMC
- PMC3196356
- OpenAlex
- W1988852098
- Cited by
- 74
- References
- 68
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 3 · 2021: 4 · 2020: 3 · 2019: 4 · 2018: 7 · 2017: 5 · 2016: 2 · 2015: 11 · 2014: 17 · 2013: 7 · 2012: 6
- FWCI
- 4.16
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (1R01MH094626-01, 1R21NS063059-01A1)
- 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, alpha4beta2 nicotinic receptor, excitatory postsynaptic potentials, hippocampal CA1, inhibitory interneurons, acetylcholine release, stratum lacunosum-moleculare, stratum oriens, nicotine withdrawal, Alzheimer's disease, optogenetics
- MeSH terms
- Channelrhodopsins, Acetylcholine, Aconitine, Animals, Biophysics, Cholinergic Fibers, Dihydro-beta-Erythroidine, Electric Stimulation, Interneurons, Light, Neural Pathways, Nicotine, Quinoxalines, Receptors, Nicotinic, Transduction, Genetic, 2-Amino-5-phosphonovalerate, Patch-Clamp Techniques, Excitatory Amino Acid Antagonists, Nicotinic Antagonists, Excitatory Postsynaptic Potentials, Diagonal Band of Broca, Mice, Optics and Photonics, CA1 Region, Hippocampal, Voltage-Sensitive Dye Imaging, In Vitro Techniques
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