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The Journal of Neuroscience, October 15, 2002, 22(20):8850-8859
Convergent Excitation of Dorsal Raphe Serotonin Neurons by
Multiple Arousal Systems (Orexin/Hypocretin, Histamine and
Noradrenaline)
Ritchie E.
Brown,
Olga A.
Sergeeva,
Krister S.
Eriksson, and
Helmut L.
Haas
Institut für Neurophysiologie,
Heinrich-Heine-Universität, D-40001 Düsseldorf, Germany
Dorsal raphe serotonin neurons fire tonically at a low rate during
waking. In vitro, however, they are not spontaneously
active, indicating that afferent inputs are necessary for tonic firing. Agonists of three arousal-related systems impinging on the dorsal raphe
(orexin/hypocretin, histamine and the noradrenaline systems) caused an
inward current and increase in current noise in whole-cell patch-clamp
recordings from these neurons in brain slices. The inward current
induced by all three agonists was significantly reduced in
extracellular solution containing reduced sodium (25.6 mM).
In extracellular recordings, all three agonists increased the firing
rate of serotonin neurons; the excitatory effects of histamine and
orexin A were occluded by previous application of phenylephrine,
suggesting that all three systems act via common effector mechanisms.
The dose-response curve for orexin B suggested an effect mediated by
type II (OX2) receptors. Single-cell PCR
demonstrated the presence of both OX1 and OX2
receptors in tryptophan hydroxylase-positive neurons. The effects of
histamine and the adrenoceptor agonist, phenylephrine, were blocked by
antagonists of histamine H1 and  1
receptors, respectively. The inward current induced by orexin A and
phenylephrine was not blocked by protein kinase inhibitors or by thapsigargin.
Three types of current-voltage responses were induced by all three
agonists but in no case did the current reverse at the potassium
equilibrium potential. Instead, in many cases the orexin A-induced
current reversed in calcium-free medium at a value ( 23 mV) consistent
with the activation of a mixed cation channel (with relative
permeabilities for sodium and potassium of 0.43 and 1, respectively).
Key words:
arousal; narcolepsy; tuberomammillary; voltage clamp; orexin; dorsal raphe
Copyright © 2002 Society for Neuroscience 0270-6474/02/22208850-10$05.00/0
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