Noradrenaline modulates transmission at a central synapse by a presynaptic mechanism.
The lateral division of the central amygdala (CeAL) is the target of ascending fibers from the pain-responsive and stress-responsive nuclei in the brainstem. We show that single fiber inputs from the nociceptive pontine parabrachial nucleus onto CeAL neurons form suprathreshold glutamatergic synapses with multiple release sites. Noradrenaline, acting at presynaptic alpha2 receptors, potently inhibits this synapse. This inhibition results from a decrease in the number of active release sites with no change in release probability. Introduction of a presynaptic scavenger of Gbetagamma subunits blocked the effects of noradrenaline, and botulinum toxin A reduced its effects, showing a direct action of betagamma subunits on the release machinery. These data illustrate a mechanism of presynaptic modulation where the output of a large multiple-release-site synapse is potently regulated by endogenously released noradrenaline and suggests that the CeA may be a target for the central nociceptive actions of noradrenaline.
The Queensland Brain Institute, The University of Queensland, QLD 4072 Australia.
Andrew J
AJ
Delaney
James W
JW
Crane
Pankaj
P
Sah
D000465:Algorithms; D000679:Amygdala / Q000503:physiopathology; D000704:Analysis of Variance; D000818:Animals; D020013:Calcium Signaling / Q000502:physiology; D002490:Central Nervous System / Q000502:physiology*; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D009412:Nerve Fibers / Q000502:physiology; D009619:Nociceptors / Q000502:physiology; D009638:Norepinephrine / Q000502:physiology*; D010146:Pain / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
D009638:Norepinephrine