Glucocorticoid enhancement of memory requires arousal-induced noradrenergic activation in the basolateral amygdala

Abstract

Considerable evidence indicates that glucocorticoid hormones enhance the consolidation of long-term memories for emotionally arousing experiences but not that for less arousing or neutral information. However, previous studies have not determined the basis of such arousal-induced selectivity. Here we report the finding that endogenous noradrenergic activation of the basolateral complex of the amygdala (BLA) induced by emotional arousal is essential in enabling glucocorticoid memory enhancement. Corticosterone administered immediately after object recognition training enhanced 24-h memory of naïve male rats but not that of rats previously habituated to the training context in order to reduce novelty-induced emotional arousal. The ␤-adrenoceptor antagonist propranolol administered either systemically or into the BLA blocked the corticosterone-induced memory enhancement. Further, in habituated rats, corticosterone activated BLA neurons, as assessed by phosphorylated cAMP response element binding (pCREB) immunoreactivity levels, and enhanced memory only when norepinephrine release was stimulated by administration of the ␣2-adrenoceptor antagonist yohimbine. These findings strongly suggest that synergistic actions of glucocorticoids and emotional arousal-induced noradrenergic activation of the BLA constitute a neural mechanism by which glucocorticoids may selectively enhance memory consolidation for emotionally arousing experiences.corticosterone ͉ emotional arousal ͉ norepinephrine ͉ object recognition ͉ memory consolidation E xtensive evidence indicates that emotionally arousing experiences are typically well remembered (1, 2). Investigations of the underlying neurobiological mechanisms suggest that glucocorticoids, released from the adrenal cortex by emotional arousal, play a key role in the strengthening of new memory traces (3-5). Recent findings of both animal and human studies suggest that glucocorticoids may selectively modulate the consolidation of memories of emotionally arousing stimuli (6-9) or those of experiences occurring during states of emotional arousal (10). Such findings imply that glucocorticoids interact with some other component of emotional arousal in influencing memory consolidation. We reported evidence that selective blockade of noradrenergic activity in the basolateral complex of the amygdala (BLA) of rats with infusions of a ␤-adrenoceptor antagonist prevented the memory-enhancing effects of glucocorticoids administered either systemically or into selected brain regions (11-13). Such findings, considered along with the evidence that emotional arousal activates the BLA (14-19) and induces the release of norepinephrine within the BLA (20, 21), suggest that emotional arousal-induced noradrenergic activation within the BLA may be essential in enabling glucocorticoid effects on memory consolidation. However, because prior experiments investigating glucocorticoid-noradrenergic interactions on memory consolidation have used training conditions that induce the release of high levels of norepineph...

Glucocorticoids in the prefrontal cortex enhance memory consolidation and impair working memory by a common neural mechanism

“…This PKA activity most likely reflects a general arousal effect rather than being a direct measure of task performance. In support of the view that glucocorticoids require arousal-associated noradrenergic activation in both increasing PKA activity and inducing cognitive effects (22), corticosterone administration to home cage control rats did not increase pPKA-s immunoreactivity levels in the mPFC (1.1% ± 3.5%; P = 0.77).…”

“…To determine whether working memory impairment and memory consolidation enhancement produced by bilateral glucocorticoid infusions are linked because of the recruitment of a common intracellular mechanism, we examined whether GR agonist effects on these two memory functions both depend on noradrenergic activity within the mPFC. We focused here on the noradrenergic system because prior evidence from our laboratory indicates that glucocorticoids crucially depend on training-induced noradrenergic activity within the BLA to enhance memory consolidation of emotionally arousing experiences (18,(21)(22)(23). Moreover, stress-induced activation of the noradrenergic system within the mPFC is known to induce working memory impairment (9), whereas a systemically administered β-adrenoceptor antagonist blocks corticosterone-induced working memory impairment (3).…”

Endocannabinoids in the rat basolateral amygdala enhance memory consolidation and enable glucocorticoid modulation of memory

“…Glucocorticoid hormones are known to enhance long-term consolidation of emotionally arousing events via often nongenomic interactions with norepinephrine and its intracellular signaling systems within the BLA (27,52). For example, it has been shown that a blockade of noradrenergic neurotransmission in the BLA with specific adrenoceptor antagonists prevents glucocorticoid effects on memory consolidation (53)(54)(55). Previous studies indicated that glucocorticoids may also interact with the endocannabinoid system.…”

A Functional Polymorphism under Positive Evolutionary Selection in ADRB2 is Associated with Human Intelligence with Opposite Effects in the Young and the Elderly

“…In addition, animal studies, show that the activation of the beta-2 receptors induce LTP in neurons in hippocampus (Hillman et al 2005a) and increase performance in tasks evaluating long-term memory and learning with the infusion of specific b2-agonists (Gibbs and Summers 2000), while b2-antagonists impaired memory consolidation (Gibbs and Summers 2005). More specifically, it has been shown that noradrenergic activation of the basolateral complex of the amygdala, involving b-adrenoreceptors, selectively enhances memory consolidation for emotionally arousing experiences (Roozendaal et al 2006). The consensus of these animal studies is that higher beta-2 adrenergic receptor activity enhances memory/learning.…”