Modulatory actions of norepinephrine on neural circuits.
A spectrum of studies has been conducted on a single aspect of NE function in which, through a beta-one receptor activation, NE appears to mediate a degree of physiological control over the gain of GABA mediated inhibition. It is significant that this single effect has been observed in numerous interrelated preparations ranging from single isolated Purkinje cells from young rats to adult Purkinje cells in awake locomoting rats. With respect to the functional conse-quences of these effects, our best current speculation as to "what NE does" is that NE acts to regulate the strength of these tuned gating mechanisms in both cerebral and cerebellar cortices. There are numerous unanswered questions raised by the past work. One pressing issue is - when and for what reason in normal function does the modulation take place? When does NE release normally occur (is it phasic or tonic), and which of the demonstrated actions appears and for how long in relation to period of receptor activation? Does NE release cause the circuit to "react" to conditions which need "improved neurocomputation" or does NE stabilize the circuit to react predictably in the face of stress? Finally, what is the molecular sequence of events between receptor activation and an alteration of GABA receptor channel opening? What additional molecular control mechanisms exist and how can the diverse inhibitory and modulatory phenomena be reconciled, both short and long term? Issues are defined which need to be clarified at all levels of the current skeleton of basic understanding. Our prediction is that pursuit of these issues will benefit from an exchange of insight gained from investigations at all levels.
Woodward
D J
DJ
University of Texas Southwestern Medical Center, Dallas.
Moises
H C
HC
Waterhouse
B D
BD
Yeh
H H
HH
Cheun
J E
JE
D000818:Animals; D002531:Cerebellum / Q000502:physiology; D015640:Ion Channel Gating / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000502:physiology*; D015290:Second Messenger Systems / Q000502:physiology; D014793:Visual Cortex / Q000502:physiology
D009638:Norepinephrine