The hippocampus mediates glucocorticoid-induced impairment of spatial memory retrieval: Dependence on the basolateral amygdala

Abstract

Previous studies have indicated that stress-activated glucocorticoid hormones induce temporary memory retrieval impairment. The present study examined whether adrenal steroid receptors in the hippocampus mediate such glucocorticoid effects on spatial memory retrieval. The specific glucocorticoid receptor (GR) agonist 11␤, 17␤-dihydroxy-6,21-dimethyl-17␣-pregna-4,6-trien-20yn-3-one (RU 28362; 5 or 15 ng) infused into the hippocampus of male Sprague-Dawley rats 60 min before water-maze retention testing, 24 h after training, dose-dependently impaired probe-trial retention performance, as assessed both by time spent in the training quadrant and initial latency to cross the platform location. The GR agonist did not affect circulating corticosterone levels immediately after the probe trial, indicating that RU 28362 infusions did not influence retention by altering glucocorticoid feedback mechanisms. As infusions of the GR agonist into the hippocampus 60 min before training did not influence water-maze acquisition or immediate recall, the findings indicated that the GR agonist-induced retention impairment was induced selectively by an influence on information retrieval. In contrast, pretest infusions of the GR agonist administered into the basolateral complex of the amygdala (BLA; 2 or 6 ng) did not alter retention performance in the water maze. However, N-methyl-D-aspartate-induced lesions of the BLA, made 1 week before training, blocked the memory retrieval impairment induced by intrahippocampal infusions of RU 28362 given 60 min before the retention test. These findings indicate that the effects of glucocorticoids on retrieval of long-term spatial memory depend on the hippocampus and, additionally, that neuronal input from the BLA is critical in enabling hippocampal glucocorticoid effects on memory retrieval.corticosterone ͉ glucocorticoid receptor ͉ stress hormone ͉ water maze I t is well established that adrenocortical hormones (corticosterone in rats, cortisol in humans) influence many aspects of cognitive performance. Studies of acute glucocorticoid effects on distinct memory phases have revealed that a single administration of glucocorticoids enhances the formation of new memories and, additionally, impairs the recall of previously learned information (1-3). Considerable evidence supports a role for the hippocampus in mediating glucocorticoid enhancement of memory consolidation. For example, either systemic or intracerebroventricular administration of glucocorticoids or specific antagonists inf luences consolidation of hippocampusdependent spatial or contextual information (4-9). Furthermore, posttraining intrahippocampal infusions of corticosterone or synthetic glucocorticoid receptor (GR) agonists enhance memory consolidation on a variety of tasks, whereas infusions of a GR antagonist or GR antisense impair memory consolidation (10-16). The basolateral complex of the amygdala (BLA; consisting of the lateral, basal, and accessory basal nuclei) is also a critical component of the neural circuitry mediating glu...

Glutamate NMDA Receptors within the Amygdala Participate in the Modulatory Effect of Glucocorticoids on Extinction of Conditioned Fear in Rats

“…Roozendaal and McGaugh found that lesions of the amygdala do not necessarily result in memory impairment but block stress hormone effects on memory consolidation. This is because the amygdala interacts with other brain regions including the hippocampus and mPFC, to regulate stress hormone effects on memory (Roozendaal et al, 2002;Roozendaal, 2003). In addition, the GABAergic intercalated cells of the amygdala, which receive input from the mPFC and control amygdala input, exhibit NMDA-dependent long-term potentiation (Royer and Pare, 2002).…”

“…Systemic administration of the glucocorticoid synthesis inhibitor metyrapone attenuated the long-term expression of contextual fear conditioning in a dose-dependent manner (Cordero et al, 2002). Roozendaal and McGaugh indicated that glucocorticoids could act directly in the amygdala to influence memory consolidation (Roozendaal and McGaugh, 1997;Roozendaal et al, 2002;Roozendaal, 2003). It is remarkable that glucocorticoids also participate in the extinction of conditioned fear.…”

Reduced Theta Coherence and P Wave Ratio Linked to Memory Deficits After Sleep Deprivation in Rat Model

“…The neural connectivity of pons with HPC, Amyg and PFC may be essential for regulation of neuronal circuits associated with sleep-related functions [52,54,60]. Impairments in performance after sleep loss could be attributed to the changes in functional connectivity in various neural networks [61,62] and it could also be due to neurons going offline at local level [63].…”

Factors That Determine the Non-Linear Amygdala Influence on Hippocampus-Dependent Memory

“…For example, it has been shown that post-training injections of the synthetic glucocorticoid dexamethasone enhanced the performance in a 48-h inhibitory avoidance retention test, and that a selective Nmethyl-d-aspartate (NMDA)-induced lesion of the BLA blocked this enhancement . In another task, intrahippocampal infusions of a glucocorticoid receptors (GRs) agonist (RU 28362) given 60 min before a spatial task retention test impaired retrieval (Roozendaal et al, 2003) and a selective NMDA-induced lesion of the BLA 1 week before training blocked this impairment. Likewise, post-training microinfusions of norepinephrine or the beta-noradrenergic antagonist propranolol into the BLA immediately following training in a spatial version of the water maze task was also shown to modulate spatial performance.…”