Paradoxical neurobehavioral rescue by cues associated with infant trauma: Amygdala 5-HT and CORT

We show that infant trauma, as modeled by infant paired odor-shock conditioning, results in later life depressive-like behavior that can be modulated by learned infant cues (i.e., odor previously paired with shock). We have previously shown that this infant attachment odor learning paradigm results in the creation of a new artificial maternal odor that is able to control pup behavior and retain its value throughout development. Here, we assess the mechanism by which this artificial maternal odor is able to rescue depressive-like behavior and show that this anti-depressant like effect results in glucocorticoid and serotonin (5-HT) related changes in amygdala gene expression and is dependent on amygdala 5-HT. Furthermore, increasing amygdala 5-HT and blocking corticosterone (CORT) in the absence of odor mimics the adult rescue effects elicited by the artificial maternal odor, suggesting a mechanism by which odor presentation exerts its repair effects.本研究表明，以婴儿气味-电击联合条件反射建模的婴儿期创伤，会导致成年后出现抑郁样行为，且该行为可通过习得的婴儿期线索（即此前与电击配对的气味）进行调控。此前我们已证实，该婴儿依恋气味学习范式可构建一种全新的人工母源气味（artificial maternal odor），该气味能够调控幼崽行为，并在整个发育过程中保持其效应价值。本研究中，我们解析了该人工母源气味能够逆转抑郁样行为的潜在机制，结果显示这类类抗抑郁效应会引发杏仁核内与糖皮质激素及血清素（5-HT）相关的基因表达变化，且该效应依赖于杏仁核内的5-HT信号。此外，在无气味存在的情况下，升高杏仁核内5-HT水平并阻断皮质酮（CORT），可模拟人工母源气味所引发的成年期挽救效应，这提示了气味呈现发挥其修复作用的潜在分子机制。