Bed nuclei of the stria terminalis modulate memory consolidation via glucocorticoid-dependent and -independent circuits

• Published in: Proceedings of the National Academy of Sciences - PNAS 2020-04, Vol.117 (14), p.8104-8114
• Main Authors: Lingg, Ryan T., Johnson, Shane B., Emmons, Eric B., Anderson, Rachel M., Romig-Martin, Sara A., Narayanan, Nandakumar S., McGaugh, James L., LaLumiere, Ryan T., Radley, Jason J.
• Format: Article
• Language: English
• Subjects: Avoidance; Biological Sciences; Consolidation; Corticosterone; Downstream effects; Emotions; Glucocorticoids; Hormones; Hypothalamus; Inhibition (psychology); Memory; Nuclei; Periaqueductal gray area; Pituitary; Pretreatment; Retention; Rodents; Stimulation; Stress; Stria terminalis; Training
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1915501117

There is extensive evidence that glucocorticoid hormones enhance memory consolidation, helping to ensure that emotionally significant events are well remembered. Prior findings suggest that the anteroventral region of bed nuclei of the stria terminalis (avBST) regulates glucocorticoid release, suggesting the potential for avBST activity to influence memory consolidation following an emotionally arousing learning event. To investigate this issue,male Sprague-Dawley rats underwent inhibitory avoidance training and repeated measurement of stress hormones, immediately followed by optogenetic manipulations of either the avBST or its projections to downstream regions, and 48 h later were tested for retention. The results indicate that avBST inhibition augmented posttraining pituitary–adrenal output and enhanced the memory for inhibitory avoidance training. Pretreatment with a glucocorticoid synthesis inhibitor blocked the memory enhancement as well as the potentiated corticosterone response, indicating the dependence of the memory enhancement on glucocorticoid release during the immediate posttraining period. In contrast, posttraining avBST stimulation decreased retention yet had no effect on stress hormonal output. Subsequent experiments revealed that inhibition of avBST input to the paraventricular hypothalamus enhanced stress hormonal output and subsequent retention, whereas stimulation did not affect either. Conversely, stimulation—but not inhibition—of avBST input to the ventrolateral periaqueductal gray impaired consolidation, whereas neithermanipulation affected glucocorticoid secretion. These findings indicate that divergent pathways from the avBST are responsible for the mnemonic effects of avBST inhibition versus stimulation and do so via glucocorticoid-dependent and -independent mechanisms, respectively.