Actions of norepinephrine in the cerebral cortex and thalamus: implications for function of the central noradrenergic system.
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.
McCormick
D A
DA
Section of Neurobiology, Yale University School of Medicine, New Haven, CT.
Pape
H C
HC
Williamson
A
A
D000200:Action Potentials / Q000187:drug effects; D000320:Adrenergic Fibers / Q000502:physiology; D001143:Arousal / Q000502:physiology*; D002412:Cations; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects; D008125:Locus Coeruleus / Q000502:physiology*; D008959:Models, Neurological; D018377:Neurotransmitter Agents / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology / Q000502:physiology*; D011941:Receptors, Adrenergic / Q000145:classification / Q000187:drug effects / Q000502:physiology; D012894:Sleep Stages / Q000502:physiology; D013788:Thalamus / Q000187:drug effects / Q000502:physiology*
D002412:Cations; D007473:Ion Channels; D018377:Neurotransmitter Agents; D011941:Receptors, Adrenergic; D009638:Norepinephrine