Urotensin II acts as a modulator of mesopontine cholinergic neurons.
Urotensin II (UII) is a vasomodulatory peptide that was not predicted to elicit CNS activity. However, because we have recently shown that the urotensin II receptor (UII-R) is selectively expressed in rat mesopontine cholinergic (MPCh) neurons, we hypothesize that UII may have a central function. The present study demonstrates that the UII system is able to modulate MPCh neuron activity. Brain slice experiments demonstrate that UII excites MPCh neurons of the mouse laterodorsal tegmentum (LDTg) by activating a slow inward current. Furthermore, microinfusion of UII into the ventral tegmental area produces a sustained increase in dopamine efflux in the nucleus accumbens, as measured by in vivo chronoamperometry. In agreement with UII activation of MPCh neurons, intracerebroventricular injections of UII significantly modulate ambulatory movements in both rats and mice but do not significantly affect startle habituation or prepulse inhibition. The present study establishes that UII is a neuromodulator that may be exploited to target disorders involving MPCh dysfunction.
Clark
Stewart D
SD
Department of Developmental and Cell Biology, University of California, Irvine, 92697-4625, USA.
Nothacker
Hans-Peter
HP
Blaha
Charles D
CD
Tyler
Christopher J
CJ
Duangdao
Dee M
DM
Grupke
Stephen L
SL
Helton
David R
DR
Leonard
Christopher S
CS
Civelli
Olivier
O
D000818:Animals; D002799:Cholinergic Fibers / Q000502:physiology*; D004594:Electrophysiology; D006185:Habituation, Psychophysiologic / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D009043:Motor Activity / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D009714:Nucleus Accumbens / Q000166:cytology / Q000502:physiology; D009924:Organ Culture Techniques; D011149:Pons / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013216:Reflex, Startle / Q000502:physiology; D013045:Species Specificity; D013681:Tegmentum Mesencephali / Q000166:cytology / Q000502:physiology; D014579:Urotensins / Q000502:physiology*
D014579:Urotensins; C029677:urotensin II