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Actions of norepinephrine in the cerebral cortex and thalamus: implications for function of the central noradrenergic system
Abstract
Norepinephrine (NE) has potent and long-lasting ionic effects on cortical and thalamic neurons. In cortical pyramidal cells, activation of beta-adrenergic receptors results in an enhanced excitability and responsiveness to depolarizing inputs. This enhanced excitability is expressed as a reduction in spike frequency adaptation and is mediated by a marked suppression of a slow Ca(++)-activated potassium current known as IAHP. In the thalamus, application of NE results in the suppression of ongoing rhythmic burst activity and a switch to the single spike firing mode of action potential generation. This effect is mediated through an alpha 1-adrenergic suppression of a resting leak potassium current, IKL, and through a beta-adrenoceptor-mediated enhancement of the hyperpolarization activated cation current Ih. Together with the actions of other neuromodulatory neurotransmitters (i.e., acetylcholine, histamine, serotonin) these effects facilitate the switch of these neurons from a state of rhythmic oscillation and low excitability during drowsiness and slow-wave sleep to a state of increased excitability and responsiveness during periods of waking, attentiveness and cognition.
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“The sedative effects of guanfacine may arise from a variety of actions, including stimulation of presynaptic α2A-receptors on noradrenergic cell bodies and terminals as well as postsynaptic α2B-receptors in the thalamus (Berridge et al., 2003; McCormick et al., 1991).”
From Catecholamine influences on prefrontal cortical function: Relevance to treatment of attention deficit/hyperactivity disorder and related disorders (2011) · cites this paper as McCormick et al., 1991
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Metadata
- Authors
- McCormick, D. A., Pape, H.-C., & Williamson, A.
- Affiliations
- Yale University (US)
- Venue
- Progress in Brain Research
- Publisher
- Elsevier
- Published
- 1991
- Volume
- 88
- Pages
- 293-305
- ISSN
- 0079-6123 (ISSN-L)
- OpenAlex
- W81520806
- Cited by
- 209
- References
- 55
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 9 · 2023: 3 · 2022: 4 · 2021: 7 · 2020: 11 · 2019: 5 · 2018: 12 · 2017: 3 · 2016: 8 · 2015: 5 · 2014: 4 · 2013: 5 · 2012: 9
- FWCI
- 2.58
- Type
- book chapter
- Language
- en
- Open access
- closed
- Locations
- Progress in brain research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Keywords
- norepinephrine, central noradrenergic system, cerebral cortex, thalamus, beta-adrenergic receptors, alpha1-adrenoceptors, cortical pyramidal neurons, spike frequency adaptation, hyperpolarization-activated current, neuronal excitability, sleep-wake cycle, neuromodulation
- MeSH terms
- Action Potentials, Adrenergic Fibers, Arousal, Cations, Cerebral Cortex, Ion Channels, Locus Coeruleus, Models, Neurological, Norepinephrine, Receptors, Adrenergic, Sleep Stages, Thalamus, Ion Channel Gating, Neurotransmitter Agents
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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