In vivo noradrenaline release evoked in the anteroventral thalamic nucleus by locus coeruleus activation: an electrochemical study

Abstract

The anteroventral thalamic nucleus is innervated by noradrenergic terminals exclusively originating in the locus coeruleus, a densely packed cell group located in the dorsotegmental part of the pons. In urethane-anaesthetized rats, electrical stimulations of locus coeruleus axons (dorsal noradrenergic bundle; 14 Hz, 20 s) evoked a rapid increase in the signal (catechol oxidation current) measured within the anteroventral thalamic nucleus by the use of carbon fibre electrodes combined with electrochemistry. This effect was reproducible and immediately reversible. Evoked changes in this current were found to be due to oxidation of noradrenaline released from terminals. The amplitude of the evoked noradrenaline release varied non-linearly with the frequency of stimulation. We investigated the influence of locus coeruleus activation on noradrenaline release measured in the anteroventral thalamic nucleus every second by means of differential pulse amperometry: (i) chemical activation of locus coeruleus by local injection of glutamate (0.2-0.8 nmol) immediately and consistently evoked noradrenaline release in a dose-dependent manner; and (ii) peripheral stimulation of the sciatic nerve (20 s)--known to enhance the firing rate of locus coeruleus neurons-evoked a noradrenaline release similar to that produced by a stimulation of the dorsal noradrenergic bundle at 8-10 Hz. Pharmacological and kinetic characteristics of the noradrenaline release were the same for central or peripheral stimulation of locus coeruleus neurons. Our results indicate that in vivo electrochemistry, because of its sensitivity and its high space and time resolution, is well suited for studies of evoked noradrenaline release from locus coeruleus terminals. This approach allowed us to describe the characteristics of central noradrenaline release evoked by central and peripheral stimulations of short duration. In particular, we observed a very close relationship between impulse flow and evoked noradrenaline release.