Endocannabinoid Signaling within the Basolateral Amygdala Integrates Multiple Stress Hormone Effects on Memory Consolidation
Endocannabinoid Signaling within the Basolateral Amygdala Integrates Multiple Stress Hormone Effects on Memory Consolidation
复制标题
DOI：
10.1038/npp.2014.334
复制
发表时间：
2015-05-01
影响因子：
7.6
通讯作者：
Roozendaal, Benno
中科院分区：
文献类型：
--
作者：
Atsak, Piray;Hauer, Daniela;Roozendaal, Benno
已知糖皮质激素与杏仁核基底外侧复合体（BLA）内的其他应激激活的神经调节系统（例如去甲肾上腺素和促肾上腺皮质激素释放因子（CRF））协同作用，以诱导情绪唤起经历的长期记忆的巩固的最佳加强。然而，由于这些糖皮质激素作用的发生往往太快，无法用基因组调控来解释，糖皮质激素如何改变去甲肾上腺素和CRF的记忆增强特性的神经生物学机制仍然难以捉摸。在这里，我们表明，内源性大麻素系统，一个快速激活的逆行信使系统，是一个主要的途径介导的作用，糖皮质激素，通过细胞表面的糖皮质激素受体，BLA神经可塑性和记忆巩固。此外，糖皮质激素在BLA内募集下游内源性大麻素活性，以与去甲肾上腺素和CRF系统相互作用，增强记忆巩固。这些发现对于理解多个应激激素系统之间的微调串扰具有重要意义，这些系统协调（不良）适应性应激和情绪唤醒对神经可塑性和记忆巩固的影响。
Glucocorticoid hormones are known to act synergistically with other stress-activated neuromodulatory systems, such as norepinephrine and corticotropin-releasing factor (CRF), within the basolateral complex of the amygdala (BLA) to induce optimal strengthening of the consolidation of long-term memory of emotionally arousing experiences. However, as the onset of these glucocorticoid actions appear often too rapid to be explained by genomic regulation, the neurobiological mechanism of how glucocorticoids could modify the memory-enhancing properties of norepinephrine and CRF remained elusive. Here, we show that the endocannabinoid system, a rapidly activated retrograde messenger system, is a primary route mediating the actions of glucocorticoids, via a glucocorticoid receptor on the cell surface, on BLA neural plasticity and memory consolidation. Furthermore, glucocorticoids recruit downstream endocannabinoid activity within the BLA to interact with both the norepinephrine and CRF systems in enhancing memory consolidation. These findings have important implications for understanding the fine-tuned crosstalk between multiple stress hormone systems in the coordination of (mal) adaptive stress and emotional arousal effects on neural plasticity and memory consolidation.