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Journal of Neuroscience, Vol 13, 3878-3883, Copyright © 1993 by Society for Neuroscience
Noradrenaline hyperpolarizes identified rat mesopontine cholinergic neurons in vitro
JA Williams and PB Reiner
Department of Psychiatry, University of British Columbia, Vancouver, Canada.
Inhibition of brainstem cholinergic neurons by noradrenergic neurons of the
locus ceruleus has long been suggested as a key mechanism of behavioral
state control. In particular, the commonly held view is that noradrenaline
(NA) plays a permissive role in rapid eye movement (REM) sleep generation
by disinhibiting brainstem cholinergic neurons. While this notion has been
supported by numerous investigations, the inhibition of cholinergic neurons
by NA has never been directly demonstrated. The purpose of this study was
to investigate the effects of NA upon identified cholinergic neurons in the
rat mesopontine tegmentum. Using whole-cell patch-clamp recordings in
slices, 175 cells were studied during bath application of 50 microM NA.
Cholinergic neurons were positively identified by intracellular labeling
with biocytin and subsequent staining with NADPH-diaphorase, a reliable
marker for brainstem cholinergic neurons (Vincent et al., 1983). Successful
intracellular labeling was obtained in 96 cells. Ninety-two percent (36 of
39) of cholinergic neurons hyperpolarized in response to NA, while
noncholinergic cells (n = 57) exhibited mixed responses. Application of NA
in a low-Ca2+, high-Mg2+ solution elicited the same hyperpolarizing effect
as in normal solution, which indicated that the effect of NA on cholinergic
neurons was direct. The noradrenergic hyperpolarization was mimicked by the
alpha 2-adrenoceptor agonist UK- 14,304, and was blocked by the alpha
2-adrenoceptor antagonist idazoxan, which suggested an alpha 2-mediated
response. Finally, voltage-clamp experiments revealed that NA activates the
inwardly rectifying potassium current, IKG.(ABSTRACT TRUNCATED AT 250
WORDS)
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