Ravenelle Rebecca, Lee Jinah, Fernandes-Henriques Carolina, Liu Jia, Friedman Allyson K, Likhtik Ekaterina, Burghardt Nesha S
Division of Systems Neuroscience, Research Foundation for Mental Hygiene, Inc., New York State Psychiatric Institute, New York, NY, USA.
Department of Psychiatry, Columbia University Irving Medical Center, New York, NY, USA.
Nat Neurosci. 2025 Aug 6. doi: 10.1038/s41593-025-02025-x.
Post-traumatic stress disorder (PTSD) is characterized by intense fear memory formation and is diagnosed more often in women than men. Here we show that increasing serotonin pharmacologically before auditory fear conditioning promoted memory recall in female and male mice, and that females were more sensitive to this effect. Optogenetic stimulation of raphe terminals in the anterior dorsal bed nucleus of the stria terminalis (adBNST) during fear conditioning increased c-Fos expression in the BNST and central nucleus of the amygdala (CeA) and enhanced fear memory recall through activation of 5-HT receptors in the adBNST in females only. Likewise, serotonin stimulation during fear learning enhanced adBNST-CeA high gamma (90-140 Hz) synchrony and adBNST-to-CeA communication in high gamma during fear memory recall in females only. These findings suggest that sex differences in the raphe-BNST-CeA pathway may contribute to the higher risk of PTSD in women.
创伤后应激障碍（PTSD）的特征是强烈恐惧记忆的形成，且女性的诊断率高于男性。我们在此表明，在听觉恐惧条件反射前通过药理学方法增加血清素可促进雌性和雄性小鼠的记忆回忆，并且雌性对此效应更为敏感。在恐惧条件反射期间对终纹床核前背侧（adBNST）中缝核终末进行光遗传学刺激，仅在雌性小鼠中增加了BNST和杏仁核中央核（CeA）中的c-Fos表达，并通过激活adBNST中的5-羟色胺受体增强了恐惧记忆回忆。同样，仅在雌性小鼠恐惧记忆回忆期间，恐惧学习过程中的血清素刺激增强了adBNST-CeA高伽马（90-140Hz）同步性以及adBNST到CeA在高伽马频段的通信。这些发现表明，中缝核-BNST-CeA通路中的性别差异可能导致女性患PTSD的风险更高。
