Institut de Neurociències, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Barcelona, Spain.
Departament de Psicobiologia i de Metodologia de les Ciències de la Salut, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Barcelona, Spain.
Sci Adv. 2024 Jul 12;10(28):eadk3365. doi: 10.1126/sciadv.adk3365. Epub 2024 Jul 10.
It remains unexplored in the field of fear memory whether functional neuronal connectivity between two brain areas is necessary for one sex but not the other. Here, we show that chemogenetic silencing of centromedial (CeM)- fibers in the lateral posterior BNST (BNSTpl) decreased fear memory consolidation in male mice but not females. Optogenetic excitation of CeM- fibers in the BNSTpl exhibited enhanced inhibitory postsynaptic currents in males compared to females. In vivo calcium imaging analysis revealed a sex-dimorphic fear memory engram in the BNSTpl. Furthermore, in humans, the single-nucleotide polymorphism (SNP) in the Tac2 receptor (rs2765) () decreased CeM-BNST connectivity in a fear task, impaired fear memory consolidation, and increased the expression of the mRNA in AA-carrier men but not in women. These sex differences in critical neuronal circuits underlying fear memory formation may be relevant to human neuropsychiatric disorders with fear memory alterations such as posttraumatic stress disorder.
在恐惧记忆领域，两个脑区之间功能性神经元连接是否对一种性别是必要的，而对另一种性别则不是，这一点仍未得到探索。在这里，我们表明，化学遗传沉默外侧后杏仁核核（BNSTpl）中的中枢（CeM）纤维会减少雄性小鼠而非雌性小鼠的恐惧记忆巩固。与雌性相比，BNSTpl 中的 CeM 纤维的光遗传兴奋表现出增强的抑制性突触后电流。体内钙成像分析显示 BNSTpl 中存在性别二态性恐惧记忆印记。此外，在人类中，Tac2 受体（rs2765）的单核苷酸多态性（SNP）在恐惧任务中降低了 CeM-BNST 的连接，损害了恐惧记忆的巩固，并增加了 AA 携带者男性而非女性中的 mRNA 的表达。这些在恐惧记忆形成的关键神经元回路中的性别差异可能与恐惧记忆改变的人类神经精神障碍有关，例如创伤后应激障碍。
