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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
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