Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Graduate Programs in Biological and Biomedical Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Nat Neurosci. 2023 Sep;26(9):1529-1540. doi: 10.1038/s41593-023-01397-2. Epub 2023 Jul 31.
Fluctuations in reproductive hormone levels are associated with mood disruptions in women, such as in postpartum and perimenopausal depression. However, the neural circuit mechanisms remain unclear. Here we report that medial preoptic area (MPOA) GABAergic neurons mediate multifaceted depressive-like behaviors in female mice after ovarian hormone withdrawal (HW), which can be attributed to downregulation of activity in Esr1 (estrogen receptor-1)-expressing GABAergic neurons. Enhancing activity of these neurons ameliorates depressive-like behaviors in HW-treated mice, whereas reducing their activity results in expression of these behaviors. Two separate subpopulations mediate different symptoms: a subpopulation projecting to the ventral tegmental area (VTA) mediates anhedonia and another projecting to the periaqueductal gray mediates immobility. These projections enhance activity of dopaminergic neurons in the VTA and serotonergic neurons in the dorsal raphe, respectively, with increased release of dopamine and serotonin, possibly through disinhibition mechanisms. Thus, the MPOA is a hub that mediates depressive-like behaviors resulting from transitions in reproductive hormone levels.
生殖激素水平的波动与女性的情绪紊乱有关，如产后和围绝经期抑郁症。然而，神经回路机制仍不清楚。在这里，我们报告内侧视前区（MPOA）GABA 能神经元介导雌性小鼠卵巢激素撤退（HW）后多方面的抑郁样行为，这可归因于表达 Esr1（雌激素受体 1）的 GABA 能神经元活性下调。增强这些神经元的活性可改善 HW 处理小鼠的抑郁样行为，而降低其活性则导致这些行为的表达。两个独立的亚群介导不同的症状：一个投射到腹侧被盖区（VTA）的亚群介导快感缺失，另一个投射到导水管周围灰质的亚群介导不动。这些投射分别增强 VTA 中的多巴胺能神经元和背侧中缝核中的 5-羟色胺能神经元的活性，导致多巴胺和 5-羟色胺的释放增加，可能通过去抑制机制。因此，MPOA 是一个枢纽，介导生殖激素水平变化引起的抑郁样行为。
