The Nicotinic Acetylcholine Receptor 5 Subunit Plays a Key Role in Attention Circuitry and Accuracy
Open accessAbstract
Stimulation of the prefrontal cortex by acetylcholine is critical for attention; however, the cellular mechanisms underlying its influence on attention pathways within the brain are not well understood. Pyramidal neurons in layer VI of the prefrontal cortex are believed to play an important role in this process because they are excited by acetylcholine and provide a major source of feedback projections to the thalamus. Here, we show using whole-cell electrophysiology that the relatively rare alpha5 subunit of the nicotinic acetylcholine receptor powerfully enhances nicotinic currents in layer VI pyramidal neurons in prefrontal cortical brain slices from adult mice. In addition, behavioral experiments using the five-choice serial reaction time test show that the presence of the nicotinic receptor alpha5 subunit also increases the accuracy of adult mice on this visual attention task under highly demanding conditions. Together, these findings demonstrate a novel and important role for the nicotinic receptor alpha5 subunit in adult brain circuitry required for attentional performance.
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nAChRs on glutamatergic thalamocortical neurons impinging on layer 5 pyramidal neurons in the prefrontal cortex are an important site for nAChR control of attention.
“Studies in rodents have also implicated nAChRs on glutamatergic thalamocortical neurons impinging on layer 5 pyramidal neurons in the prefrontal cortex as an important site for nAChR control of attention (Lambe et al. 2005;Bailey et al. 2010).”
From Mechanisms of Nicotine Addiction (2021) · cites this paper as Bailey et al. 2010
The Introduction and Discussion support a role for prefrontal nAChRs in attention. But this paper identifies nAChRs on layer VI pyramidal neurons that project from cortex to thalamus; it does not establish the claimed site on thalamocortical neurons impinging on layer 5 pyramidal neurons. No page numbers were provided in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredInclusion of α5 into α4β2* nAChRs decreases the extent of desensitization.
“For example, inclusion of the α5 subunit into α4β2* nAChRs decreases the extent of desensitization (Bailey et al. 2010).”
From Nicotine Withdrawal (2015) · cites this paper as Bailey et al. 2010
The Results section ('The α5 nicotinic subunit protects against desensitization') reports about half as much nicotine-induced desensitization in wild-type mouse layer VI neurons as in α5−/− neurons. The claim omits that cellular and exposure context; the Discussion notes that earlier work in reduced preparations found the opposite effect. (LLM, conf=0.86)
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References 80 · Cited by 146
- Authors
- Bailey, C. D. C., De Biasi, M., Fletcher, P. J., & Lambe, E. K.
- Affiliations
- University of Toronto (CA)
- Centre for Addiction and Mental Health (CA)
- Corresponding author
- Lambe, E. K.
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2010-07-07
- Volume
- 30
- Issue
- 27
- Pages
- 9241-9252
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3004929
- OpenAlex
- W2041556105
- Cited by
- 146
- References
- 80
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 7 · 2023: 6 · 2022: 4 · 2021: 5 · 2020: 12 · 2019: 4 · 2018: 10 · 2017: 8 · 2016: 14 · 2015: 13 · 2014: 22 · 2013: 13 · 2012: 13
- FWCI
- 4.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canada Research Chairs
- Canadian Institutes of Health Research (89825_1, MOP89825, 83422_1, 89825)
- National Institute on Drug Abuse (R01DA017173)
- 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 › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- nicotinic acetylcholine receptors, alpha5 subunit, prefrontal cortex, acetylcholine, attention, thalamocortical feedback
- MeSH terms
- Acetylcholine, Analysis of Variance, Anesthetics, Local, Animals, Attention, Choice Behavior, Dihydro-beta-Erythroidine, Dose-Response Relationship, Drug, gamma-Aminobutyric Acid, Membrane Potentials, Mice, Inbred C57BL, Motor Activity, Nerve Net, Neuropsychological Tests, Nicotine, Photic Stimulation, Reaction Time, Receptors, Nicotinic, Tetrodotoxin, Prefrontal Cortex, Pyramidal Cells, Mice, Knockout, Patch-Clamp Techniques, Cholinergic Agents, Nicotinic Agonists, Nicotinic Antagonists, Mice, In Vitro Techniques
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