Basolateral amygdala noradrenergic influence enables enhancement of memory consolidation induced by hippocampal glucocorticoid receptor activation

Abstract

Previously, we reported that bilateral excitotoxic lesions of the basolateral nucleus of the amygdala ( There is considerable evidence that the basolateral nucleus of the amygdala (BLA) is critically involved in regulating the consolidation of different forms of memory, including explicit͞ declarative memory. Many findings indicate that this amygdala nucleus mediates the memory-modulatory effects of adrenal stress hormones released by emotional arousal (1, 2). Findings of several recent studies from our laboratory indicate that posttraining infusions of the specific glucocorticoid receptor (GR or type II) agonist RU 28362 administered into the BLA induce dose-dependent enhancement of inhibitory avoidance retention (3) and that excitotoxic lesions of the BLA induced before training block the memory-enhancing effects of systemically administered glucocorticoids (4) as well as the memory-impairing effects induced by adrenalectomy (5, 6). BLA lesions also block the memory-enhancing effects of the GR agonist administered directly into the hippocampus (7). These findings suggest that BLA neuronal activity modulates stress-induced memory consolidation processes in, or involving, the hippocampus and are consistent with the view that the BLA is not a locus of memory storage but regulates consolidation processes in other brain regions (2).Extensive evidence indicates that noradrenergic and cholinergic systems in the amygdala participate in modulating memory consolidation (8-13). Although the activation of these two neurotransmitter systems in the BLA may occur under different experimental conditions (14, 15) and induce slightly differential electrophysiological responses in BLA neurons (16-18), they have highly comparable effects on memory consolidation. Posttraining infusion of either a ␤-adrenoceptor or muscarinic cholinergic agonist into the amygdala enhances inhibitory avoidance retention (11,12,19,20), and inactivation of either receptor type in the BLA blocks the memoryenhancing effects of systemic glucocorticoids (ref. 13; and A.E.P., B.R. and J.L.M, unpublished observation). Moreover, previous findings indicate that the BLA is a critical locus of interaction between glucocorticoids and the noradrenergic system in memory consolidation modulation (13, 21).The present experiments examined whether ␤-adrenoceptor or muscarinic cholinergic receptor activation in the BLA is critically involved in enabling facilitation of memory consolidation induced by activation of GRs in the hippocampus. In the first experiment, rats received unilateral microinfusions into the BLA of either the ␤-adrenoceptor antagonist atenolol or the muscarinic cholinergic antagonist atropine 10 min prior to training in an inhibitory avoidance task. The GR agonist RU 28362 was administered ipsilaterally into the dorsal hippocampus immediately after training, and retention was tested 48 h later. In a second experiment, we examined whether BLAhippocampus interactions in memory consolidation involve unilateral projections between these brain reg...

Basolateral amygdala projections to ventral hippocampus modulate the consolidation of footshock, but not contextual, learning in rats

“…It has been hypothesized that the BLA plays this more general role, at least in part, through interactions with distinct regions (McGaugh 2002(McGaugh , 2004McIntyre et al 2012). BLA connections with forebrain regions such as the hippocampus and striatum that are selectively involved in the consolidation of certain kinds of memories (McDonald 1991;Pitkänen et al 2000;McGaugh 2002;Malin and McGaugh 2006;Paz et al 2006;Chavez et al 2013) suggest that efferent pathways from the BLA may be selectively involved in modulating consolidation for specific kinds of information.Indeed, much evidence suggests that the BLA interacts with the hippocampus during memory consolidation (Packard et al 1994;Roozendaal et al 1999;Malin and McGaugh 2006) and that the BLA directly or indirectly influences activity and plasticity in different parts of the hippocampal formation (Ikegaya et al 1995;Frey et al 2001;McIntyre et al 2005;McReynolds et al 2014;Lovitz and Thompson 2015). These findings suggest pathway mechanisms by which the BLA influences the consolidation of memories regulated by the hippocampal formation.…”

“…Indeed, much evidence suggests that the BLA interacts with the hippocampus during memory consolidation (Packard et al 1994;Roozendaal et al 1999;Malin and McGaugh 2006) and that the BLA directly or indirectly influences activity and plasticity in different parts of the hippocampal formation (Ikegaya et al 1995;Frey et al 2001;McIntyre et al 2005;McReynolds et al 2014;Lovitz and Thompson 2015). These findings suggest pathway mechanisms by which the BLA influences the consolidation of memories regulated by the hippocampal formation.…”

Intrahippocampal infusions of anisomycin produce amnesia: Contribution of increased release of norepinephrine, dopamine, and acetylcholine

“…Studies examining injections of other drugs into the hippocampus often reveal inverted U doseresponse functions with impairments evident at high doses (Quevedo et al 1998;Stefani and Gold 1998;Roozendaal et al 1999;Goshen et al 2007;Hein et al 2007). Therefore, it is likely that the large increases in release of the neurotransmitters measured here, and presumably other neurotransmitters as well, are sufficient to produce amnesia.…”

The Corticosteroid Receptor Hypothesis of Depression

“…In this context, it is important to note that such effects do not solely result from altered corticosteroid effects in the hippocampus. For example, GR-mediated memory consolidation is also influenced by ␤ -adrenoceptor stimulation in the amygdala (Roozendaal et al 1999).…”