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Cited by 248Nicotinic Acetylcholine Receptors StudyNeuroscience and Neuropharmacology ResearchReceptor Mechanisms and Signaling

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Nicotinic Receptor Activation in Human Cerebral Cortical Interneurons: a Mechanism for Inhibition and Disinhibition of Neuronal Networks

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Alkondon, Manickavasagom, Pereira, Edna F. R., Eisenberg, Howard M., Albuquerque, Edson X.·2000·The Journal of Neuroscience
DOI 10.1523/jneurosci.20-01-00066.2000PMC PMC6774099
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Abstract

Cholinergic control of the activity of human cerebral cortical circuits has long been thought to be accounted for by the interaction of acetylcholine (ACh) with muscarinic receptors. Here we report the discovery of functional nicotinic receptors (nAChRs) in interneurons of the human cerebral cortex and discuss the physiological and clinical implications of these findings. The whole-cell mode of the patch-clamp technique was used to record responses triggered by U-tube application of the nonselective agonist ACh and of the α7-nAChR-selective agonist choline to interneurons visualized by means of infrared-assisted videomicroscopy in slices of the human cerebral cortex. Choline induced rapidly desensitizing whole-cell currents that, being sensitive to blockade by methyllycaconitine (MLA; 50 n m), were most likely subserved by an α7-like nAChR. In contrast, ACh evoked slowly decaying whole-cell currents that, being sensitive to blockade by dihydro-β-erythroidine (DHβE; 10 μ m), were most likely subserved by an α4β2-like nAChR. Application of ACh (but not choline) to the slices also triggered GABAergic postsynaptic currents (PSCs). Evidence is provided that ACh-evoked PSCs are the result of activation of α4β2-like nAChRs present in preterminal axon segments and/or in presynaptic terminals of interneurons. Thus, nAChRs can relay inhibitory and/or disinhibitory signals to pyramidal neurons and thereby modulate the activity of neuronal circuits in the human cerebral cortex. These mechanisms, which appear to be retained across species, can account for the involvement of nAChRs in cognitive functions and in certain neuropathological conditions.

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Metadata

Authors
Alkondon, M., Pereira, E. F. R., Eisenberg, H. M., & Albuquerque, E. X.
Affiliations
  • University of Maryland, Baltimore (US)
  • Universidade Federal do Rio de Janeiro (BR)
ORCID
Venue
The Journal of Neuroscience
Publisher
Society for Neuroscience
Published
2000-01-01
Volume
20
Issue
1
Pages
66-75
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
DOI
10.1523/jneurosci.20-01-00066.2000
PMC
PMC6774099
OpenAlex
W1939947624
Cited by
248
References
6
Citations by year
2025: 1 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 4 · 2019: 3 · 2018: 10 · 2017: 5 · 2016: 4 · 2015: 8 · 2014: 6 · 2013: 12 · 2012: 10
FWCI
9.05
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01es005730-07)
  • U.S. Public Health Service
  • National Institute of Neurological Disorders and Stroke (R01NS025296, NS 25296)
  • National Institute of Environmental Health Sciences (ES 05730)
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 › Receptor Mechanisms and Signaling
Keywords
nicotinic acetylcholine receptors, alpha7 nicotinic acetylcholine receptor, alpha4beta2 nicotinic receptor, cholinergic modulation, acetylcholine, choline, presynaptic nicotinic receptors, neuronal inhibition, disinhibition, human cerebral cortex, methyllycaconitine, dihydro-beta-erythroidine, cognitive function, neuropathology
MeSH terms
Acetylcholine, Aconitine, Adolescent, Adult, Bicuculline, Cerebral Cortex, Child, Choline, Dihydro-beta-Erythroidine, Female, gamma-Aminobutyric Acid, Humans, Insecticides, Interneurons, Male, Middle Aged, Nerve Net, Neural Inhibition, Organ Culture Techniques, Receptors, Nicotinic, Stimulation, Chemical, Tetrodotoxin, Quisqualic Acid, Patch-Clamp Techniques, Excitatory Amino Acid Agonists, GABA Antagonists, Excitatory Postsynaptic Potentials, alpha7 Nicotinic Acetylcholine Receptor

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