Noradrenaline release in the locus coeruleus modulates memory formation and consolidation; roles for α- and β-adrenergic receptors

Abstract

Noradrenaline, essential for the modulation of memory, is released in various parts of the brain from nerve terminals controlled by the locus coeruleus (LoC). Noradrenaline release consequent upon input from higher brain areas also occurs within the LoC itself. We examined the effect of noradrenaline on adrenergic receptors in the LoC on memory processing, using colored bead discrimination learning in the young domestic chick. We have shown previously that the release of noradrenaline in the hippocampus and cortex (mesopallium) is essential for acquisition and consolidation of short-term to intermediate and to long-term memory. Noradrenaline release within the LoC is triggered by the glutamatergic input from the forebrain. Inhibition by LoC injection of NMDA or AMPA receptor antagonists is rescued by injection of β2-and β3-adrenoceptor (AR) agonists in the hippocampus. We show that inhibition of α2A-ARs by BRL44408 in the LoC up to 30 min post-training consolidates weakly-reinforced learning. Conversely activation of α2A-ARs in the LoC at the times of consolidation between short-term and intermediate and long-term memory caused memory loss, which is likely to be due to a decreased release of noradrenaline within these two time windows. The α2A-AR antagonist will block presynaptic inhibitory receptors leading to an increase in extracellular noradrenaline. This interpretation is supported by the actions of noradrenaline uptake blockers that produce the same memory outcome. BRL44408 in the mesopallium also caused memory enhancement. β2-ARs are important in the first time window, whereas α1-, α2C-and β3-ARs are important in the second time window. The results reveal that for successful memory formation noradrenaline release is necessary within the LoC as well as in other brain regions, at the time of consolidation of memory from short-term to intermediate and from intermediate to long-term memory.