Journal of Neuroscience ( IF 4.4 ) Pub Date : 2024-11-13 , DOI: 10.1523/jneurosci.0844-24.2024 Timothy D. Skog, Shane B. Johnson, Dalton C. Hinz, Ryan T. Lingg, Emily N. Schulz, Jordan T. Luna, Terry G. Beltz, Sara A. Romig-Martin, Stephanie C. Gantz, Baojian Xue, Alan K. Johnson, Jason J. Radley
The activation of autonomic and hypothalamo-pituitary-adrenal (HPA) systems occurs interdependently with behavioral adjustments under varying environmental demands. Nevertheless, laboratory rodent studies examining the neural bases of stress responses have generally attributed increments in these systems to be monolithic, regardless of whether an active or passive coping strategy is employed. Using the shock probe defensive burying test (SPDB) to measure stress-coping features naturalistically in male and female rats, we identify a neural pathway whereby activity changes may promote distinctive response patterns of hemodynamic and HPA indices typifying active and passive coping phenotypes. Optogenetic excitation of the rostral medial prefrontal cortex (mPFC) input to the ventrolateral periaqueductal gray (vlPAG) decreased passive behavior (immobility), attenuated the glucocorticoid hormone response, but did not prevent arterial pressure and heart rate increases associated with rats’ active behavioral (defensive burying) engagement during the SPDB. In contrast, inhibition of the same pathway increased behavioral immobility and attenuated hemodynamic output but did not affect glucocorticoid increases. Further analyses confirmed that hemodynamic increments occurred preferentially during active behaviors and decrements during immobility epochs, whereas pathway manipulations, regardless of the directionality of effect, weakened these correlational relationships. Finally, neuroanatomical evidence indicated that the influence of the rostral mPFC->vlPAG pathway on coping response patterns is mediated predominantly through GABAergic neurons within vlPAG. These data highlight the importance of this prefrontal->midbrain connection in organizing stress-coping responses and in coordinating bodily systems with behavioral output for adaptation to aversive experiences.
中文翻译:
前额叶 > 导水管灰色通路差异参与压力应对反应的自主神经、激素和行为特征
自主神经和下丘脑-垂体-肾上腺 (HPA) 系统的激活与不同环境需求下的行为调整相互依赖。然而,检查压力反应神经基础的实验室啮齿动物研究通常将这些系统的增量归因于整体,无论采用主动还是被动应对策略。使用休克探针防御性埋葬试验 (SPDB) 自然地测量雄性和雌性大鼠的压力应对特征,我们确定了一条神经通路,其中活动变化可能会促进血流动力学和 HPA 指数的独特反应模式,这些指数代表主动和被动应对表型。对腹外侧导水管周围灰质 (vlPAG) 输入的喙内侧前额叶皮层 (mPFC) 的光遗传学兴奋减少了被动行为(不动),减弱了糖皮质激素反应,但不能阻止与大鼠在 SPDB 期间的主动行为(防御性埋葬)参与相关的动脉压和心率增加。相比之下,抑制同一途径增加了行为不动并减弱了血流动力学输出,但不影响糖皮质激素的增加。进一步的分析证实,血流动力学增加优先发生在主动行为期间,而在不动时期期间血流动力学增加优先发生,而无论效应的方向性如何,通路操作都会削弱这些相关关系。最后,神经解剖学证据表明,喙部 mPFC->vlPAG 通路对应对反应模式的影响主要通过 vlPAG 内的 GABA 能神经元介导。 这些数据强调了这种前额叶 %3 脑连接在组织压力应对反应和协调身体系统与行为输出以适应厌恶体验方面的重要性。