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Second messenger-mediated actions of norepinephrine on target neurons in central circuits: a new perspective on intracellular mechanisms and functional consequences
Journal article   Peer reviewed

Second messenger-mediated actions of norepinephrine on target neurons in central circuits: a new perspective on intracellular mechanisms and functional consequences

B D Waterhouse, F M Sessler, W Liu and C S Lin
Progress in brain research, v 88(C), pp 351-362
1991
PMID: 1667548

Abstract

Norepinephrine - pharmacology Synapses - drug effects Norepinephrine - physiology Rats Receptors, Adrenergic, beta - physiology Brain - physiology gamma-Aminobutyric Acid - physiology Cyclic AMP - physiology Potassium - physiology Animals Neurons - physiology Synaptic Transmission - drug effects Models, Neurological Neurons - drug effects Chlorides - physiology Action Potentials - drug effects Second Messenger Systems Ion Channel Gating - drug effects
Ever since the initial demonstration of a widespread distribution of noradrenergic fibers to functionally diverse regions of the mammalian forebrain, there has been considerable interest in determining the electrophysiological effects of norepinephrine (NE) on individual neurons within these target areas. While early studies showed that NE could directly inhibit cell firing via increased intracellular levels of cyclic AMP, more recent work has revealed a spectrum of noradrenergic actions, which are more accurately characterized as neuromodulatory. More specifically, numerous experimental conditions have been described where NE at levels subthreshold for producing direct depressant effects on spontaneous firing can facilitate neuronal responses to both excitatory and inhibitory synaptic stimuli. The goal of this report is to review recent evidence which suggests that the various modulatory actions of NE on central neurons result from the activation of different adrenoceptor-linked second messenger systems. In particular, we have focused on the candidate signal transduction mechanisms that may underlie NE's ability to augment cerebellar and cortical neuronal responsiveness to GABAergic synaptic inputs. The consequences of such NE-induced changes in synaptic efficacy are considered not only with respect to their influences on feature extraction properties of individual sensory cortical neurons but also with regard to the potential impact such actions would have on the signal processing capabilities of a network of noradrenergically innervated cortical cells.

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