Falconi-Sobrinho Luiz Luciano, Anjos-Garcia Tayllon Dos, Rebelo Macário Arosti, Hernandes Paloma Molina, Almada Rafael Carvalho, Tanus-Santos Jose Eduardo, Coimbra Norberto Cysne
Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo (USP), Av. Bandeirantes 3900, Ribeirão Preto, São Paulo, 14049-900, Brazil; Behavioural Neurosciences Institute (INeC), Psychobiology Division, Av. Bandeirantes, 3900, Ribeirão Preto, 14049-900, São Paulo, Brazil.
Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo (USP), Av. Bandeirantes 3900, Ribeirão Preto, São Paulo, 14049-900, Brazil; Biomedical Sciences Institute of the Federal University of Alfenas (UNIFAL), Alfenas, Minas Gerais, Brazil.
Neuropharmacology. 2024 Mar 1;245:109831. doi: 10.1016/j.neuropharm.2023.109831. Epub 2023 Dec 30.
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.
前扣带回皮质（ACC）的Cg1（24b）区域调节由下丘脑组织的谷氨酸介导的无条件恐惧和抗伤害感受。然而，24b区域是否也通过与导水管周围灰质背侧（dPAG）的连接来调节这些防御反应仍不清楚，dPAG是一个与先天恐惧诱导防御的发生有关的中脑结构。这项工作的目的是研究在受到蛇威胁的雄性C57BL/6小鼠中，向ACC内微量注射溶剂、N-甲基-D-天冬氨酸（NMDA，1纳摩尔）或利多卡因（2%）的行为效应与dPAG中Fos蛋白表达和一氧化氮能活性之间的相关性。此外，还通过神经束追踪程序对24b区域-dPAG通路进行了表征。最后，研究了在24b区域用NMDA处理前10分钟，用神经元型一氧化氮合酶抑制剂N（ω）-丙基-L-精氨酸（NPLA；0.2、0.4或0.8纳摩尔）预处理dPAG对受威胁小鼠行为和伤害感受反应的影响。24b区域N-甲基-D-天冬氨酸受体的激活促进了逃避和僵住，而不是风险评估，并增强了dPAG中的Fos表达和亚硝酸盐水平，而利多卡因则降低了逃避和风险评估以及dPAG中的Fos和一氧化氮能活性。此外，用NPLA预处理dPAG可抑制24b区域内NMDA促进的惊恐效应，同时增加伤害感受。将顺行神经示踪剂注入24b区域显示轴突纤维围绕着背内侧和背外侧PAG的核周体。在将逆行神经示踪剂注入dPAG后，在24b区域鉴定出了神经元。我们的研究结果表明，ACC/24b区域通过募集dPAG一氧化氮能神经元来调节先天防御反应。
