The anterior cingulate cortex (ACC) Cg1 (24b) area modulates glutamate-mediated unconditioned fear and antinociception organised by hypothalamus. However, it remains unknown whether 24b area also modulates these latter defensive responses through connections with the dorsal periaqueductal grey matter (dPAG), a midbrain structure implicated in the genesis of innate fear-induced defence. The aim of this work is to examine the correlation between the behavioural effects of intra-ACC microinjections of vehicle, NMDA (1 nmol) or lidocaine (2%) with Fos protein expression and nitrergic activity in the dPAG of male C57BL/6 mice that were threatened by snakes. In addition, the 24b area-dPAG pathways were also characterised by neural tract tracing procedures. Finally, the effect of dPAG pretreatment with the neuronal nitric oxide synthase inhibitor N(omega)-propyl-l-arginine (NPLA; 0.2, 0.4 or 0.8 nmol) 10 min before 24b area treatment with NMDA on behavioural and nociceptive responses of threatened mice was studied. The activation of 24b area N-methyl-d-aspartic acid receptors facilitated escape and freezing rather than risk assessment, and enhanced Fos expression and nitrite levels in dPAG, while lidocaine decreased escape and risk assessment as well as Fos and nitrergic activity in dPAG. In addition, dPAG pretreatment with NPLA suppressed intra-24b NMDA-facilitated panicogenic effects while increased nociception. Infusions of an antegrade neurotracer into 24b area showed axonal fibres surrounding both dorsomedial and dorsolateral PAG perikarya. Neurons were identified in 24b area after deposits of a retrograde neurotracer into dPAG. Our findings suggest that the ACC/24b area modulates innate defensive responses through the recruitment of dPAG nitrergic neurons.

前扣带皮层 (ACC) Cg1 (24b) 区域调节谷氨酸介导的无条件恐惧和下丘脑组织的镇痛作用。然而，目前尚不清楚 24b 区域是否也通过与背侧导水管周围灰质(dPAG) 的连接来调节后一种防御反应，dPAG 是一种与先天恐惧诱导防御的起源有关的中脑结构。这项工作的目的是检查 ACC 内显微注射媒介物、NMDA (1 nmol) 或利多卡因 (2%) 的行为效应与雄性 C57BL/6 小鼠 dPAG 中Fos 蛋白表达和硝能活性之间的相关性，受到蛇的威胁。此外，还通过神经束示踪程序对 24b 区域-dPAG 通路进行了表征。最后，在用 NMDA 处理 24b 区域之前 10 分钟，用神经元一氧化氮合酶抑制剂 N(omega)-丙基-l-精氨酸（NPLA；0.2、0.4 或 0.8 nmol）预处理 dPAG 对受威胁小鼠的行为和伤害性反应被研究了。24b区N-甲基-d-天冬氨酸受体的激活促进了逃逸和冻结而不是风险评估，并且增强了dPAG中的Fos表达和亚硝酸盐水平，而利多卡因降低了逃逸和风险评估以及dPAG中的Fos和硝化活性。此外，用 NPLA 预处理 dPAG 抑制了 24b 内 NMDA 促进的恐慌效应，同时增加了伤害感受。将顺行神经示踪剂输注到 24b 区域显示了背内侧和背外侧 PAG 核周周围的轴突纤维。将逆行神经示踪剂沉积到 dPAG 后，在 24b 区域中鉴定出神经元。我们的研究结果表明 ACC/24b 区域通过招募 dPAG硝能神经元来调节先天防御反应。