Basolateral amygdala-nucleus accumbens interactions in mediating glucocorticoid enhancement of memory consolidation

Abstract

Systemic or intracerebral administration of glucocorticoids enhances memory consolidation in several tasks. Previously, we reported that these effects depend on an intact basolateral nucleus of the amygdala (BLA) and efferents from the BLA that run through the stria terminalis (ST). The BLA projects directly to the nucleus accumbens (NAc) via this ST pathway. The NAc also receives direct projections from the hippocampus and, therefore, may be a site of convergence of BLA and hippocampal influences in modulating memory consolidation. In support of this view, we found previously that lesions of either the NAc or the ST also block the memory-modulatory effect of systemically administered glucocorticoids. The present experiments examined the effects of lesions of the NAc or the ST on the memory-modulatory effects of intracerebral glucocorticoids on inhibitory avoidance training. Microinfusions of the specific glucocorticoid receptor agonist 11beta,17beta-dihydroxy-6,21-dimethyl-17alpha-pregna-4,6-trien-20yn-3-one (RU 28362; 1.0 or 3.0 ng) into either the BLA or the hippocampus of male Sprague Dawley rats administered immediately after training enhanced the 48 hr retention performance in a dose-dependent manner. Bilateral lesions of the NAc or the ST alone did not affect retention performance but blocked the memory enhancement induced by intra-BLA or intrahippocampal glucocorticoid receptor agonist administration. These findings indicate that the BLA-NAc pathway plays an essential role in mediating glucocorticoid effects on memory consolidation and suggest that the BLA interacts with hippocampal effects on memory consolidation via this pathway.

Fig. 1.

Representative photomicrographs illustrating placement of cannula in the basolateral amygdala (A) or dorsal hippocampus (B). BLA, Basolateral nucleus of the amygdala; CA1, CA3, Ammon's horn;CEA, central nucleus of the amygdala;DG, dentate gyrus; OT, optic tract.

Fig. 2.

A, Maximum (gray-shaded area) and minimum (black-shaded area) extents of the nucleus accumbens lesions. Plates are adapted from the atlas of Paxinos and Watson (1997). B, Representative nucleus accumbens lesion.Arrows denote lesion borders. C, Sham-lesioned control. AC, Anterior limb of the anterior commissure; ec, external capsule;LV, lateral ventricle.

Fig. 3.

A, Maximum (gray-shaded area) and minimum (black-shaded area) extents of the stria terminalis lesions. Plates are adapted from the atlas of Paxinos and Watson (1997). B, Representative stria terminalis lesion.Arrows denote lesion borders. C, Sham-lesioned control. CA3, Ammon's horn;DG, dentate gyrus; Fi, fimbria;LV, lateral ventricle; ST, stria terminalis.

Fig. 4.

Step-through latencies (mean ± SEM) for the 48 hr retention test of rats with lesions of either the nucleus accumbens (A) or the stria terminalis (B) given microinfusions of vehicle or the specific glucocorticoid receptor agonist RU 28362 (1.0 or 3.0 ng in 0.2 μl) into the basolateral amygdala immediately after inhibitory avoidance training. **p < 0.01 compared with the corresponding vehicle group; ♦p < 0.05 compared with the corresponding sham-lesion group (n = 7–15 per group). N., Nucleus.

Fig. 5.

Step-through latencies (mean ± SEM) for the 48 hr retention test of rats with lesions of either the nucleus accumbens (A) or the stria terminalis (B) given microinfusions of vehicle or the specific glucocorticoid receptor agonist RU 28362 (1.0 or 3.0 ng in 0.5 μl) into the dorsal hippocampus immediately after inhibitory avoidance training. *p < 0.05 compared with the corresponding vehicle group; ♦p < 0.05 compared with the corresponding sham-lesion group (n = 7–14 per group). N., Nucleus.