Astrocytic adrenoceptors and learning: alpha1-adrenoceptors

Abstract

Noradrenergic receptors are expressed on both on astrocytes and neurons and noradrenergic activation of astrocytic beta(2)- and beta(3)-adrenoceptors are necessary for memory consolidation. In this paper, we marshal evidence for astrocytic alpha(1)-adrenoceptor involvement in memory consolidation. We examine the role of alpha(1)-adrenoceptors in hippocampal and mesopallial (cortical) memory processing using a discriminative avoidance task in the day-old chick. The selective alpha(1)-adrenoceptor agonist, methoxamine, caused the consolidation of weakly-reinforced memory at the time of transition of short-term to intermediate memory and at the time of transition of intermediate to long-term memory. The selective antagonist prazosin prevented memory consolidation at these two times. Blockade of memory by injection of an alpha(2)-adrenoceptor agonist into the LoC could be overcome by mesopallial or hippocampal injection of alpha(1)-, beta(2)- and beta(3)-adrenoceptor agonists. The results of studies where we challenged the ability of methoxamine to promote consolidation by pre-administration of astrocytic metabolic inhibitors of glycogenolysis or oxidative metabolism, suggest that the alpha(1)-adrenoceptor effect is astrocytic. This conclusion is supported by the finding that co-administration of suboptimal doses of methoxamine and thrombin have an additive effect on promoting consolidation. Thrombin causes a calcium response in cultured chick astrocytes but not in neurons. Thrombin, like methoxamine, promotes consolidation at the transition points between short-term, intermediate memory and long-term memory stages. Thrombin enhancement of memory consolidation is blocked by an alpha(1)-adrenoceptor antagonist but not by antagonists of beta(2)- or beta(3)-adrenoceptors. In summary, noradrenaline activation of alpha(1)-adrenoceptors is necessary for consolidation from both short-term and intermediate memory in both the hippocampus and the mesopallium in the chick. Evidence is presented suggesting that the memory consolidating action of alpha(1)-adrenoceptor stimulation results from receptors located on astroctyes and involves an increase in free cytosolic calcium from internal stores.