Department of Integrative Physiology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
Science. 2020 Mar 6;367(6482):1105-1112. doi: 10.1126/science.aaz4639.
The mechanism by which psychological stress elicits various physiological responses is unknown. We discovered a central master neural pathway in rats that drives autonomic and behavioral stress responses by connecting the corticolimbic stress circuits to the hypothalamus. Psychosocial stress signals from emotion-related forebrain regions activated a VGLUT1-positive glutamatergic pathway from the dorsal peduncular cortex and dorsal tenia tecta (DP/DTT), an unexplored prefrontal cortical area, to the dorsomedial hypothalamus (DMH), a hypothalamic autonomic center. Genetic ablation and optogenetics revealed that the DP/DTT→DMH pathway drives thermogenic, hyperthermic, and cardiovascular sympathetic responses to psychosocial stress without contributing to basal homeostasis. This pathway also mediates avoidance behavior from psychosocial stressors. Given the variety of stress responses driven by the DP/DTT→DMH pathway, the DP/DTT can be a potential target for treating psychosomatic disorders.
心理压力引发各种生理反应的机制尚不清楚。我们在大鼠中发现了一条中央主神经通路，通过将皮质边缘应激回路连接到下丘脑，驱动自主和行为应激反应。来自情绪相关前脑区域的社会心理压力信号激活了来自背侧被盖脚蹼和背侧被盖穹窿（DP/DTT）的 VGLUT1 阳性谷氨酸能通路，这是一个未被探索的前额叶皮质区域，到下丘脑的背内侧（DMH），一个自主的下丘脑中心。遗传消融和光遗传学揭示了 DP/DTT→DMH 通路驱动热原性、发热和心血管交感反应对社会心理压力，而不贡献于基础体内平衡。该通路还介导了对社会心理应激源的回避行为。鉴于 DP/DTT→DMH 通路驱动的各种应激反应，DP/DTT 可能是治疗身心障碍的潜在靶点。
