Kim Woonhee, Chung ChiHye
Department of Biological Sciences, Konkuk University, Seoul, South Korea.
FASEB J. 2024 Dec 15;38(24):e70275. doi: 10.1096/fj.202402296RR.
The prevalence of depressive disorders in women has been reported in many countries. However, the cellular mechanisms mediating such sex differences in stress susceptibility remain largely unknown. Previously, we showed that lateral habenula (LHb) neurons are more activated in female mice than in male mice by restraint stress. Given the important role of LHb in depressive disorders, we aimed to investigate the synaptic differences between male and female LHb and to examine the possible impact of the estrous cycle on neurotransmission in LHb. We found that the passive and active properties of LHb neurons differed according to the estrous cycle. Spontaneous excitatory postsynaptic currents exhibited higher amplitudes during the diestrus stage and lower frequencies in females than in males, whereas inhibitory postsynaptic currents showed no significant differences. Acute stress-induced hyperpolarization of resting membrane potentials (RMP) was observed in both sexes, with notable changes in female silent and tonic neurons. Stress exposure eliminated estrous cycle-dependent RMP differences and introduced cycle-specific excitability changes, especially in the metestrus and diestrus stages, suggesting that the hormonal cycle may set the synaptic tone of the LHb, thus modulating stress responses in females. Our study provides invaluable groundwork for understanding the detailed interaction between the estrous cycle and stress exposure in female LHb.
许多国家都报道了女性抑郁症的患病率。然而，介导这种应激易感性性别差异的细胞机制在很大程度上仍不清楚。此前，我们发现，束缚应激使雌性小鼠外侧缰核（LHb）神经元的激活程度高于雄性小鼠。鉴于LHb在抑郁症中的重要作用，我们旨在研究雄性和雌性LHb之间的突触差异，并探讨发情周期对LHb神经传递的可能影响。我们发现，LHb神经元的被动和主动特性因发情周期而异。雌性小鼠在动情后期自发兴奋性突触后电流的幅度较高，频率低于雄性，而抑制性突触后电流没有显著差异。在两性中均观察到急性应激诱导的静息膜电位（RMP）超极化，雌性沉默神经元和紧张性神经元有明显变化。应激暴露消除了发情周期依赖性的RMP差异，并引入了特定周期的兴奋性变化，尤其是在发情后期和动情后期，这表明激素周期可能设定了LHb的突触基调，从而调节雌性的应激反应。我们的研究为理解雌性LHb中发情周期与应激暴露之间的详细相互作用提供了宝贵的基础。
